D H Phillips

Summary

Affiliation: Institute of Cancer Research
Country: UK

Publications

  1. ncbi request reprint Standardization and validation of DNA adduct postlabelling methods: report of interlaboratory trials and production of recommended protocols
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Mutagenesis 14:301-15. 1999
  2. ncbi request reprint N-demethylation accompanies alpha-hydroxylation in the metabolic activation of tamoxifen in rat liver cells
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton SM2 5NG, UK
    Carcinogenesis 20:2003-9. 1999
  3. ncbi request reprint Methods of DNA adduct determination and their application to testing compounds for genotoxicity
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton, United Kingdom
    Environ Mol Mutagen 35:222-33. 2000
  4. ncbi request reprint Polycyclic aromatic hydrocarbons in the diet
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Mutat Res 443:139-47. 1999
  5. ncbi request reprint Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer
    David H Phillips
    Institute of Cancer Research, Haddow Laboratory, Sutton, Surrey, United Kingdom
    Environ Mol Mutagen 39:143-9. 2002
  6. ncbi request reprint Understanding the genotoxicity of tamoxifen?
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Carcinogenesis 22:839-49. 2001
  7. ncbi request reprint Smoking-related DNA and protein adducts in human tissues
    David H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Carcinogenesis 23:1979-2004. 2002
  8. ncbi request reprint Genotoxicity of human mammary lipid
    F L Martin
    Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 56:5342-6. 1996
  9. ncbi request reprint Determination of the enzymes responsible for activation of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline in the human breast
    J A Williams
    Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Pharmacogenetics 8:519-28. 1998
  10. ncbi request reprint Activation of genotoxins to DNA-damaging species in exfoliated breast milk cells
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG, Surrey, UK
    Mutat Res 470:115-24. 2000

Detail Information

Publications89

  1. ncbi request reprint Standardization and validation of DNA adduct postlabelling methods: report of interlaboratory trials and production of recommended protocols
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Mutagenesis 14:301-15. 1999
    ..Use of these standards and procedures has reduced interlaboratory variability in quantitation of DNA adducts...
  2. ncbi request reprint N-demethylation accompanies alpha-hydroxylation in the metabolic activation of tamoxifen in rat liver cells
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton SM2 5NG, UK
    Carcinogenesis 20:2003-9. 1999
    ..Detection of tamoxifen-related DNA adducts by (32)P-postlabelling is achieved with >90% labelling efficiency...
  3. ncbi request reprint Methods of DNA adduct determination and their application to testing compounds for genotoxicity
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Sutton, United Kingdom
    Environ Mol Mutagen 35:222-33. 2000
    ..While there may be adduct levels at which there is no observable biological effect, there are at present insufficient data on which to set a threshold level for biological significance...
  4. ncbi request reprint Polycyclic aromatic hydrocarbons in the diet
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Mutat Res 443:139-47. 1999
    ..More recently, biomonitoring procedures have been developed to assess human exposure to PAHs and these have also indicated that diet is a major source of exposure. Exposure to nitro-PAHs through food consumption appears to be very low...
  5. ncbi request reprint Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer
    David H Phillips
    Institute of Cancer Research, Haddow Laboratory, Sutton, Surrey, United Kingdom
    Environ Mol Mutagen 39:143-9. 2002
    ..The agents responsible for the activity in milk appear to be moderately polar lipophilic compounds and of low molecular weight. Identification of these agents and their sources may hold clues to the origins of breast cancer...
  6. ncbi request reprint Understanding the genotoxicity of tamoxifen?
    D H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Carcinogenesis 22:839-49. 2001
    ..This article reviews the current evidence for genotoxic mechanisms for tamoxifen carcinogenicity, and discusses some inconsistencies in the data...
  7. ncbi request reprint Smoking-related DNA and protein adducts in human tissues
    David H Phillips
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton SM2 5NG, UK
    Carcinogenesis 23:1979-2004. 2002
    ..This paper reviews the literature on smoking-related DNA and protein adducts in human tissues and shows how such studies have provided mechanistic insight into the epidemiological associations between smoking and cancer...
  8. ncbi request reprint Genotoxicity of human mammary lipid
    F L Martin
    Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 56:5342-6. 1996
    ..Bacterial mutagenicity correlated with micronucleus-forming activity in a metabolically competent mammalian cell line (MCL-5). This genotoxic activity merits further investigation in relation to the etiology of breast cancer...
  9. ncbi request reprint Determination of the enzymes responsible for activation of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline in the human breast
    J A Williams
    Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Pharmacogenetics 8:519-28. 1998
    ..Our results indicate possible mechanisms for the metabolic activation of dietary carcinogens in the human breast...
  10. ncbi request reprint Activation of genotoxins to DNA-damaging species in exfoliated breast milk cells
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG, Surrey, UK
    Mutat Res 470:115-24. 2000
    ..The results suggest that breast milk is a valuable source of human mammary cells for the study of the metabolic activation of possible carcinogens...
  11. ncbi request reprint DNA damage in human breast milk cells and its induction by 'early' and 'late' milk extracts
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Carcinogenesis 21:799-804. 2000
    ..Cells isolated from milk activated the rodent mammary carcinogens o-toluidine and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The relevance of genotoxic exposures to breast cancer initiation requires further investigation...
  12. ncbi request reprint Pathways of heterocyclic amine activation in the breast: DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) formed by peroxidases and in human mammary epithelial cells and fibroblasts
    J A Williams
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Mutagenesis 15:149-54. 2000
    ..5 and 14.8 adducts/10(8) nucleotides (mean values), respectively. Our results indicate the possible contribution of stromal cells and breast peroxidases to the metabolic activation of carcinogens in the mammary gland...
  13. ncbi request reprint Interindividual variation in the metabolic activation of heterocyclic amines and their N-hydroxy derivatives in primary cultures of human mammary epithelial cells
    E M Stone
    Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Carcinogenesis 19:873-9. 1998
    ..This appears to be the first pilot study to demonstrate interindividual variations in the metabolic activation of heterocyclic amines and their metabolic intermediates in primary cultures of HMECs in vitro...
  14. ncbi request reprint The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures
    S Z Al-Buheissi
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Prostate 66:876-85. 2006
    ..Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT)...
  15. ncbi request reprint Morphological transformation of C3H/M2 mouse fibroblasts by extracts of human mammary lipid
    F L Martin
    Haddow Laboratories, Institute of Cancer Research, Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom
    Biochem Biophys Res Commun 251:182-9. 1998
    ..Median comet tail lengths (induced with MLEs of 8.0 g-lipid equivalent) ranged from 6.0 to 74.0 micrometer. The results demonstrate the presence of as-yet-unidentified transforming agents in mammary lipid...
  16. ncbi request reprint Idoxifene derivatives are less reactive to DNA than tamoxifen derivatives, both chemically and in human and rat liver cells
    M R Osborne
    Section of Molecular Carcinogenesis, Haddow Laboratories, Sutton, Surrey, UK
    Carcinogenesis 20:293-7. 1999
    ..All these results indicate that idoxifene is much less genotoxic than tamoxifen, and should therefore be a safer drug...
  17. ncbi request reprint 4-Hydroxytamoxifen gives DNA adducts by chemical activation, but not in rat liver cells
    M R Osborne
    Section of Molecular Carcinogenesis, Haddow Laboratories, and CRC Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG
    Chem Res Toxicol 12:151-8. 1999
    ..12 mmol kg-1) with the same substances. If 4-hydroxytamoxifen is metabolized to 4, alpha-dihydroxytamoxifen in rat liver, then either this substance is not converted to reactive esters or they are rapidly detoxified...
  18. ncbi request reprint Primary cultures of prostate cells and their ability to activate carcinogens
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey, UK
    Prostate Cancer Prostatic Dis 5:96-104. 2002
    ..This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP...
  19. ncbi request reprint Genotoxicity of human breast milk from different countries
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Mutagenesis 16:401-6. 2001
    ..More work is required to confirm these initial findings and to examine their relevance to variations in breast cancer incidence...
  20. ncbi request reprint The DNA repair inhibitors hydroxyurea and cytosine arabinoside enhance the sensitivity of the alkaline single-cell gel electrophoresis ('comet') assay in metabolically-competent MCL-5 cells
    F L Martin
    Institute of Cancer Research, Haddow Laboratories, Cotswold Rd, Sutton, UK
    Mutat Res 445:21-43. 1999
    ..Many more agents need to be tested in order to determine how well the comet assay using MCL-5 cells (or modified versions of it) can distinguish genotoxins from non-genotoxins...
  21. ncbi request reprint The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA-binding species in rat hepatocytes proceeds via sulphation
    W Davis
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
    Carcinogenesis 19:861-6. 1998
    ..It is concluded that the activation of tamoxifen in rat liver cells to DNA binding products proceeds predominantly through hydroxylation followed by sulphate ester formation at the alpha-position of the ethyl side chain...
  22. ncbi request reprint Generation of putative intrastrand cross-links and strand breaks in DNA by transition metal ion-mediated oxygen radical attack
    D R Lloyd
    Section of Molecular Carcinogenesis, Haddow Laboratories, Sutton, Surrey, U K
    Chem Res Toxicol 10:393-400. 1997
    ..The results demonstrate that generation of the putative intrastrand cross-links and strand breaks in DNA, mediated by Fenton reactions, occurs by independent mechanisms...
  23. ncbi request reprint Resolution of alpha-hydroxytamoxifen; R-isomer forms more DNA adducts in rat liver cells
    M R Osborne
    Section of Molecular Carcinogenesis, Haddow Laboratories, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Chem Res Toxicol 14:888-93. 2001
    ..They have the same chemical properties but, on treatment of rat hepatocytes in culture, R-(+)-alpha-hydroxytamoxifen gave at least eight times as many DNA adducts as the S-(-)-isomer...
  24. pmc Tumorigenicity of a combination of psoriasis therapies
    D H Phillips
    Haddow Laboratories, Institute of Cancer Research, Belmont, Sutton, Surrey, UK
    Br J Cancer 69:1043-5. 1994
    ..This finding has implications for the use of both agents in combination in the treatment of psoriasis...
  25. ncbi request reprint Comparison of the formation of 8-hydroxy-2'-deoxyguanosine and single- and double-strand breaks in DNA mediated by fenton reactions
    D R Lloyd
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey SM2 5NG, U K
    Chem Res Toxicol 11:420-7. 1998
    ..Furthermore, the generation of 8-OHdG exhibits a good correlation with the formation of double-strand breaks, suggesting that they arise by a similar mechanism...
  26. ncbi request reprint Diversity of TMPRSS2-ERG fusion transcripts in the human prostate
    J Clark
    Institute of Cancer Research, Male Urological Cancer Research Centre, Sutton, Surrey, UK
    Oncogene 26:2667-73. 2007
    ....
  27. ncbi request reprint The role of the N-(hydroxymethyl)melamines as antitumour agents: mechanism of action studies
    H M Coley
    Department of Drug Development, Institute of Cancer Research, Belmont, Sutton, Surrey, U K
    Biochem Pharmacol 49:1203-12. 1995
    ..As the precise mechanism of action for the N-(hydroxymethyl)melamines is apparently not shared by many commonly used anticancer agents, this may confer their broad-spectrum activity versus heavily pretreated tumours...
  28. ncbi request reprint N-Acetyltransferases, sulfotransferases and heterocyclic amine activation in the breast
    J A Williams
    Institute of Cancer Research, Haddow Laboratories, Sutton, UK
    Pharmacogenetics 11:373-88. 2001
    ..Western blot analysis of mammary cytosolic protein showed detectable levels of SULT1A1 and SULT1A3...
  29. ncbi request reprint Preparation of a methylated DNA standard, and its stability on storage
    M R Osborne
    Molecular Carcinogenesis Section, Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Chem Res Toxicol 13:257-61. 2000
    ..The half-life for loss of 7-methylguanine at neutral pH was estimated to be 70 h at 39 degrees C, 460 h at 22 degrees C, 3800 h at 10 degrees C, and about 4 years at -20 degrees C...
  30. ncbi request reprint Formation and persistence of DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in target and non-target organs after intratracheal instillation in rats
    Christian A Bieler
    Division of Molecular Toxicology, German Cancer Research Center, INF 280, 69120 Heidelberg, Germany
    Carcinogenesis 28:1117-21. 2007
    ..The correlation between DNA adducts in lung and blood suggests that persistent 3-NBA-DNA adducts in the blood may be useful biomarkers for human respiratory exposure to 3-NBA...
  31. pmc Time- and concentration-dependent changes in gene expression induced by benzo(a)pyrene in two human cell lines, MCF-7 and HepG2
    Sarah L Hockley
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    BMC Genomics 7:260. 2006
    ....
  32. ncbi request reprint Growth kinetics in MCF-7 cells modulate benzo[a]pyrene-induced CYP1A1 up-regulation
    Haiyan Jiao
    Biomedical Sciences Unit, Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    Mutagenesis 22:111-6. 2007
    ....
  33. ncbi request reprint DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver
    Nan Mei
    Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA
    Mutat Res 602:83-91. 2006
    ..Although the same treatment does not produce tumors in rat liver, it does induce DNA adducts and mutations in this tissue, albeit at lower levels than in kidney...
  34. ncbi request reprint The environmental pollutant and carcinogen 3-nitrobenzanthrone and its human metabolite 3-aminobenzanthrone are potent inducers of rat hepatic cytochromes P450 1A1 and -1A2 and NAD(P)H:quinone oxidoreductase
    Marie Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
    Drug Metab Dispos 34:1398-405. 2006
    ....
  35. ncbi request reprint N-Acetyltransferase and sulfotransferase activity in human prostate: potential for carcinogen activation
    Salah Z Al-Buheissi
    Institute of Cancer Research, Section of Molecular Carcinogenesis, Sutton, UK
    Pharmacogenet Genomics 16:391-9. 2006
    ..N-Acetyltransferases (NATs) and sulfotransferases (SULTs) are key phase II metabolizing enzymes that can be involved both in the detoxification and in the activation of many human promutagens and procarcinogens...
  36. ncbi request reprint Molecular mechanism of genotoxicity of the environmental pollutant 3-nitrobenzanthrone
    Marie Stiborova
    Department of Biochemistry, Charles University, Albertov 2030, 12840 Prague 2, Czech Republic
    Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 149:191-7. 2005
    ..The results suggest that both CYPs and peroxidases may play an important role in metabolism of 3-ABA to reactive species forming DNA adducts, participating in genotoxicity of this compound and its parental counterpart, 3-NBA...
  37. ncbi request reprint Sex differences in risk of lung cancer: Expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts
    Steen Mollerup
    Department of Toxicology, National Institute of Occupational Health, Oslo, Norway
    Int J Cancer 119:741-4. 2006
    ..0001) irrespective of smoking-status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to lung cancer among females...
  38. ncbi request reprint Tamoxifen-DNA adduct formation in human endometrium
    Frederick A Beland
    Chem Res Toxicol 18:1507-9; author reply 1509-11. 2005
  39. ncbi request reprint Identification of three major DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenine
    Volker M Arlt
    Institute of Cancer Research, Section of Molecular Carcinogenesis, Sutton, Surrey, United Kingdom
    Int J Cancer 118:2139-46. 2006
    ....
  40. ncbi request reprint Polymorphisms of DNA repair genes and risk of non-small cell lung cancer
    Shanbeh Zienolddiny
    Department of Toxicology, National Institute of Occupational Health, Oslo, Norway
    Carcinogenesis 27:560-7. 2006
    ....
  41. ncbi request reprint Interleukin 1 receptor antagonist gene polymorphism and risk of lung cancer: a possible interaction with polymorphisms in the interleukin 1 beta gene
    Helge Lind
    Department of Toxicology, National Institute of Occupational Health, P O Box 8149 Dep, N 0033 Oslo, Norway
    Lung Cancer 50:285-90. 2005
    ..62 and T/T 5.87; 2.15-16.05). Furthermore, IL1RN*1 carriers had nearly two-fold higher levels of bulky/hydrophobic DNA adducts in the lung. Our findings support the significance of IL1 gene cluster polymorphisms and risk of lung cancer...
  42. ncbi request reprint Aristolochic acid mutagenesis: molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK
    Carcinogenesis 28:2253-61. 2007
    ....
  43. ncbi request reprint Mutagenicity and DNA adduct formation by the urban air pollutant 2-nitrobenzanthrone
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom
    Toxicol Sci 98:445-57. 2007
    ....
  44. doi request reprint Mutagenic potential of nitrenium ions of nitrobenzanthrones: correlation between theory and experiment
    Jóhannes Reynisson
    School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom
    Environ Mol Mutagen 49:659-67. 2008
    ..Therefore, our data clearly indicate that the stability of the nitrenium ions is one critical determinant of the mutagenic potency of NBAs in Salmonella tester strains...
  45. doi request reprint Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in human endometrium
    Maneesh N Singh
    Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston, UK
    Toxicology 249:85-90. 2008
    ..Whether this is evidence that generation of genotoxic tamoxifen metabolites may occur in human endometrial tissue remains to be ascertained...
  46. pmc The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo
    Lauren A Courter
    Department of Environmental and Molecular Toxicology, Oregon State University, Agricultural and Life Sciences 1007, Corvallis, OR 97331, USA
    Cancer Lett 265:135-47. 2008
    ..Therefore we validate microarray data as a source to uncover transcriptional signatures that may provide insights into molecular pathways affected following exposure to environmental complex mixtures such as diesel exhaust particulates...
  47. doi request reprint DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis
    Fabrizio Veglia
    Life Sciences and Epidemiology Unit, ISI Foundation, Torino 10133, Italy
    Carcinogenesis 29:932-6. 2008
    ..The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years...
  48. doi request reprint The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity
    Marie Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
    Toxicology 247:11-22. 2008
    ..These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential...
  49. doi request reprint p53-dependent global nucleotide excision repair of cisplatin-induced intrastrand cross links in human cells
    Sara Bhana
    Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK
    Mutagenesis 23:131-6. 2008
    ..Given the frequency of p53 mutations in human tumours, these results may have implications for the use of cisplatin in cancer chemotherapy...
  50. doi request reprint Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Carcinogenesis 29:656-65. 2008
    ..7- to 2.6-fold) relative to WT mice. These data reveal an apparent paradox, whereby hepatic CYP enzymes appear to be more important for detoxification of BaP in vivo, despite being involved in its metabolic activation in vitro...
  51. ncbi request reprint Smoking and breast cancer: is there really a link?
    David H Phillips
    Cancer Epidemiol Biomarkers Prev 17:1-2. 2008
  52. ncbi request reprint The 32P-postlabeling assay for DNA adducts
    David H Phillips
    Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Nat Protoc 2:2772-81. 2007
    ..It has a wide range of applications in human, animal and in vitro studies, and can be used for a wide variety of classes of compound and for the detection of adducts formed by complex mixtures. This protocol can be completed in 3 d...
  53. ncbi request reprint Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: studies with the hepatic NADPH:cytochrome P450 reductase null mouse
    Marie Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
    Toxicol Appl Pharmacol 226:318-27. 2008
    ....
  54. ncbi request reprint AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell lines
    Sarah L Hockley
    Section of Molecular Carcinogenesis, The Institute of Cancer Research, Surrey, UK
    Chem Res Toxicol 20:1797-810. 2007
    ..Promoter analysis identified candidate genes for direct transcriptional regulation by either AHR or p53. These analyses have further dissected and characterized the complex cellular response to BaP...
  55. ncbi request reprint Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53
    Sarah L Hockley
    Section of Molecular Carcinogenesis, The Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Carcinogenesis 29:202-10. 2008
    ..Taken together, these results give further insight into the role of p53 in the response of human cells to BaP and BPDE and suggest that loss of this tumour suppressor can influence the metabolic activation of BaP...
  56. ncbi request reprint DNA adduct formation in human hepatoma cells treated with 3-nitrobenzanthrone: analysis by the (32)P-postlabeling method
    Takaharu Kanno
    Frontier Science Innovation Center, Osaka Prefecture University, Osaka, Japan
    Mutat Res 634:184-91. 2007
    ..Quantitative analyses revealed that the major adduct was dA3'p-N(6)-C2-ABA and its relative adduct labeling (RAL) value at 36.4 microM of 3-NBA was 200.8+/-86.1/10(8)nucleotide...
  57. doi request reprint Gene expression profiles modulated by the human carcinogen aristolochic acid I in human cancer cells and their dependence on TP53
    Maria L Simões
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey, UK
    Toxicol Appl Pharmacol 232:86-98. 2008
    ..These results strengthen the importance of TP53 in AA-induced cancer, and indicate that other alterations, e.g. to MYC oncogenic pathways, may also contribute...
  58. ncbi request reprint Early proximal tubule injury in experimental aristolochic acid nephropathy: functional and histological studies
    Catherine Lebeau
    Laboratory for Research on Peptide Metabolism, Faculty of Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    Nephrol Dial Transplant 20:2321-32. 2005
    ..Clinical and in vitro findings have previously suggested that the proximal tubule was the target of AA...
  59. ncbi request reprint Synthesis, characterization, and 32p-postlabeling analysis of DNA adducts derived from the environmental contaminant 3-nitrobenzanthrone
    Martin R Osborne
    Section of Molecular Carcinogenesis and Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Chem Res Toxicol 18:1056-70. 2005
    ..Therefore, a different approach to the synthesis of authentic standards is needed for the structural characterization of 3-NBA-derived DNA adducts formed in vivo...
  60. ncbi request reprint Analysis of tamoxifen-DNA adducts in endometrial explants by MS and 32P-postlabeling
    Frederick A Beland
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
    Biochem Biophys Res Commun 320:297-302. 2004
    ..Tamoxifen-DNA adducts were not detected by either method...
  61. ncbi request reprint Stereoselective metabolic activation of alpha-hydroxy-N-desmethyltamoxifen: the R-isomer forms more DNA adducts in rat liver cells
    Martin R Osborne
    Section of Molecular Carcinogenesis, Brookes Lawley Building, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Chem Res Toxicol 17:697-701. 2004
    ..This suggests that the R-isomer more readily undergoes sulfate conjugation to generate a reactive carbocation that attacks DNA...
  62. ncbi request reprint DNA adducts and mutagenic specificity of the ubiquitous environmental pollutant 3-nitrobenzanthrone in Muta Mouse
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Surrey, United Kingdom
    Environ Mol Mutagen 43:186-95. 2004
    ..These results suggest that G:C-->T:A transversions induced by 3-NBA are caused by misreplication of adducted guanine residues through incorporation of adenine opposite the adduct (A-rule)...
  63. ncbi request reprint Activation of 3-nitrobenzanthrone and its metabolites to DNA-damaging species in human B lymphoblastoid MCL-5 cells
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
    Mutagenesis 19:149-56. 2004
    ..Environmental exposure to 3-NBA may be a health hazard for large sections of the population and the risks associated with such exposure require further assessment...
  64. ncbi request reprint Human enzymes involved in the metabolic activation of the environmental contaminant 3-nitrobenzanthrone: evidence for reductive activation by human NADPH:cytochrome p450 reductase
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom
    Cancer Res 63:2752-61. 2003
    ..These results demonstrate for the first time the potential of human NADPH: p450 reductase and recombinant p450s to contribute to the metabolic activation of 3-NBA by nitroreduction...
  65. ncbi request reprint Activation of 3-nitrobenzanthrone and its metabolites by human acetyltransferases, sulfotransferases and cytochrome P450 expressed in Chinese hamster V79 cells
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Int J Cancer 105:583-92. 2003
    ..Consequently, polymorphisms in these genes could be important determinants of lung cancer risk from 3-NBA...
  66. ncbi request reprint Effects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chinese-herb nephropathy
    Frédéric Debellé
    Laboratoire de Recherche sur le Métabolisme des Peptides L R M P, Faculte de Medecine, Universite Libre de Bruxelles, 1070, Brussels, Belgium
    Arch Toxicol 77:218-26. 2003
    ..These functional and histological data suggest that DXF does not enhance AA nephrotoxicity in a rat model for CHN. Further investigations are needed to clarify the mechanism by which DXF may enhance AA-DNA adduct formation...
  67. ncbi request reprint Mutagenic fingerprint of ozone in human cells
    Soraia A C Jorge
    Laboratory of Genetic Instability and Cancer, UPR 2169 CNRS, Institute of Cancer Research, 7 rue Guy Moquet, B P 8, 94801 Villejuif, Cedex, France
    DNA Repair (Amst) 1:369-78. 2002
    ..Possible applications derived from our results with respect to ozone genotoxicity should help determining quantifiable biomarkers of ozone exposure in human health, especially for carcinogenesis...
  68. ncbi request reprint DNA adduct formation by the ubiquitous environmental pollutant 3-nitrobenzanthrone and its metabolites in rats
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Biochem Biophys Res Commun 300:107-14. 2003
    ..Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation...
  69. ncbi request reprint Metabolic activation of the environmental contaminant 3-nitrobenzanthrone by human acetyltransferases and sulfotransferase
    Volker M Arlt
    Institute of Cancer Research, Section of Molecular Carcinogenesis, Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Carcinogenesis 23:1937-45. 2002
    ..Moreover, the yet-unidentified four major 3-NBA-derived adducts may be DNA adducts without an N-acetyl group...
  70. ncbi request reprint Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians' Health Cohort Study
    Frederica P Perera
    Division of Environmental Health Sciences, Joseph L Mailman School of Public Health, Columbia University, New York City, NY 10032, USA
    Carcinogenesis 23:1641-6. 2002
    ..The findings underscore the complex and important role of biological susceptibility as a determinant of risk from carcinogens found in tobacco smoke and other environmental compounds...
  71. ncbi request reprint Electrospray ionization-tandem mass spectrometry and 32P-postlabeling analyses of tamoxifen-DNA adducts in humans
    Frederick A Beland
    Division of Biochemical Toxicology, HFT 110, National Center for Toxicological Research, 3900 NCTR Rd, Jefferson, AR 72079, USA
    J Natl Cancer Inst 96:1099-104. 2004
    ..However, these findings have been controversial. We used electrospray ionization-tandem mass spectrometry (ES-MS/MS) and 32P-postlabeling analyses to investigate the presence of tamoxifen-DNA adducts in human endometrial tissue...
  72. ncbi request reprint Inter-individual differences in the ability of human milk-fat extracts to enhance the genotoxic potential of the procarcinogen benzo[a]pyrene in MCF-7 breast cells
    Olga I Kalantzi
    Department of Environmental Science, IENS, Lancaster University, Lancaster, UK
    Environ Sci Technol 38:3614-22. 2004
    ..No identifiable pollutants were present in these fractions. The results suggest that different environmental pollutants present in human tissue may influence the susceptibility of target cells to initiating events...
  73. ncbi request reprint Role of estrogen receptor in regulation of polycyclic aromatic hydrocarbon metabolic activation in lung
    Gisle Berge
    Department of Toxicology, National Institute of Occupational Health, PO Box 8149 Dep, N 0033 Oslo, Norway
    Lung Cancer 45:289-97. 2004
    ..In conclusion, the present data do not support the hypothesis of a role of estrogen or the ERalpha in regulating the metabolic activation of polycyclic aromatic hydrocarbons in lung...
  74. ncbi request reprint A biomarker model of sublethal genotoxicity (DNA single-strand breaks and adducts) using the sentinel organism Aporrectodea longa in spiked soil
    Francis L Martin
    Department of Biological Sciences, Institute of Environmental and Natural Sciences, Lancaster University, Lancaster LA1 4YQ, UK
    Environ Pollut 138:307-15. 2005
    ..This preliminary investigation suggests that earthworm tissues may be incorporated into genotoxicity assays to facilitate hazard identification within terrestrial ecosystems...
  75. ncbi request reprint Organ specificity of DNA adduct formation by tamoxifen and alpha-hydroxytamoxifen in the rat: implications for understanding the mechanism(s) of tamoxifen carcinogenicity and for human risk assessment
    David H Phillips
    Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK
    Mutagenesis 20:297-303. 2005
    ..The confinement of ST2A2, the isozyme of hydroxysteroid sulfotransferase that can activate the compounds, mainly to rat liver is the possible reason for the formation of ducts in the liver but not in other organs of the rat...
  76. ncbi request reprint DNA adducts as markers of exposure and risk
    David H Phillips
    Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, UK
    Mutat Res 577:284-92. 2005
    ....
  77. ncbi request reprint Bioactivation of 3-aminobenzanthrone, a human metabolite of the environmental pollutant 3-nitrobenzanthrone: evidence for DNA adduct formation mediated by cytochrome P450 enzymes and peroxidases
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG, UK
    Cancer Lett 234:220-31. 2006
    ..Collectively, these results suggest that both CYPs and peroxidases may play an important role in metabolizing 3-ABA to reactive DNA adduct forming species...
  78. ncbi request reprint DNA adduct formation by the environmental contaminant 3-nitrobenzanthrone after intratracheal instillation in rats
    Christian A Bieler
    German Cancer Research Center, Division of Molecular Toxicology, Heidelberg, Germany
    Int J Cancer 116:833-8. 2005
    ..Therefore, 3-NBA-DNA adducts present in the blood are useful biomarkers for exposure to 3-NBA and may help to assess the effective biological dose in humans exposed to it...
  79. ncbi request reprint Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Cancer Res 65:2644-52. 2005
    ..Collectively, these results show the role of human hepatic NQO1 to reduce 3-NBA to species being further activated by NATs and SULTs...
  80. ncbi request reprint The proteolytic release of genotoxins from cooked beef
    Francis L Martin
    Haddow Laboratories, Institute of Cancer Research, Cotswold Rd, Sutton, Surrey SM2 5NG, UK
    Biochem Biophys Res Commun 293:1497-501. 2002
    ..Proteolysis released significant amounts of DNA-damaging material that was not extractible prior to enzymic digestion, suggesting that human exposures to diet-derived genotoxins may have been underestimated...
  81. ncbi request reprint 3-aminobenzanthrone, a human metabolite of the environmental pollutant 3-nitrobenzanthrone, forms DNA adducts after metabolic activation by human and rat liver microsomes: evidence for activation by cytochrome P450 1A1 and P450 1A2
    Volker M Arlt
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Chem Res Toxicol 17:1092-101. 2004
    ..In summary, our results strongly suggest a genotoxic potential of 3-ABA for humans. Moreover, 3-ABA is not only a suitable biomarker of exposure to 3-NBA but may also directly contribute to the high genotoxic potential of 3-NBA...
  82. ncbi request reprint Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods
    Laura J Schild
    Carcinogen DNA Interactions Section, National Cancer Institute, Building 37, Room 4032 NIH, 37 Convent Drive MSC 4255, Bethesda, MD 20892 4255, USA
    Mutagenesis 20:115-24. 2005
    ..The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed...
  83. ncbi request reprint 32P-postlabeling analysis of DNA adducts
    David H Phillips
    Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK
    Methods Mol Biol 291:3-12. 2005
    ....
  84. ncbi request reprint Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha- and AP-1-dependent pathway
    Caroline H Arnott
    Cancer Research UK Translational Oncology Laboratory, Bart s and The London School of Medicine and Dentistry, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK
    Oncogene 21:4728-38. 2002
    ..This may be one mechanism by which chronic inflammation increases susceptibility to cancer...
  85. ncbi request reprint Smoking-related DNA adducts in anal epithelium
    David H Phillips
    Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK
    Mutat Res 560:167-72. 2004
    ..00001, Fisher's exact test). These results indicate that components of tobacco smoke inflict genotoxic damage in the anal epithelium of smokers and provide a plausible mechanism for a causal association between smoking and anal cancer...
  86. ncbi request reprint Msh2 deficiency increases susceptibility to benzo[a]pyrene-induced lymphomagenesis
    Shanbeh Zienolddiny
    Department of Toxicology, National Institute of Occupational Health, Oslo, Norway
    Int J Cancer 118:2899-902. 2006
    ..In summary, the results suggest that B[a]P accelerates lymphomagenesis in Msh2-deficient mice. Furthermore, Msh2 deficiency does not have any significant effect on B[a]P-DNA adduct levels...
  87. ncbi request reprint p53 tumour suppressor gene and the tobacco industry
    David H Phillips
    Lancet 365:1026; author reply 1026-7. 2005
  88. ncbi request reprint Modulation of N-methyl-N-nitrosourea-induced crypt restricted metallothionein immunopositivity in mouse colon by a non-genotoxic diet-related chemical
    Eilish T Donnelly
    Department of Surgery, Cancer Centre, Queen s University Belfast, Belfast BT12 6BJ, Northern Ireland, UK
    Carcinogenesis 25:847-55. 2004
    ..This study has shown that exposure to a non-genotoxic diet-related compound (lambdaCgN) modulates the effective NOC dosimetry for induction of MT crypt restricted immunopositivity...
  89. ncbi request reprint Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies
    Gaëlle Gillerot
    Division of Nephrology and Department of Pathology, Université Catholique de Louvain Medical School, Brussels, Belgium
    Kidney Int 64:1883-92. 2003
    ..Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain...