acetoxyacetylaminofluorene

Summary

Summary: An alkylating agent that forms DNA ADDUCTS at the C-8 position in GUANINE, resulting in single strand breaks. It has demonstrated carcinogenic action.

Top Publications

  1. Rzeszowska Wolny J, Widłak P. Damaged DNA-binding proteins: recognition of N-acetoxy-acetylaminofluorene-induced DNA adducts. Acta Biochim Pol. 1999;46:173-80 pubmed
  2. Busch D, van Vuuren H, de Wit J, Collins A, Zdzienicka M, Mitchell D, et al. Phenotypic heterogeneity in nucleotide excision repair mutants of rodent complementation groups 1 and 4. Mutat Res. 1997;383:91-106 pubmed
  3. Wolf S, Vouros P. Incorporation of sample stacking techniques into the capillary electrophoresis CF-FAB mass spectrometric analysis of DNA adducts. Anal Chem. 1995;67:891-900 pubmed
    ..The techniques have been applied to the analysis of adducts formed in the in vitro reaction of N-acetoxy-N-acetyl-2-aminofluorene with DNA...
  4. Ho Y, Lin J. Preferential promutagenic lesions at exons 7-8 of human p53 genomic DNA induced by the direct-acting hepatocarcinogens N-nitroso-2-acetylaminofluorene and N-acetoxy-2-acetylaminofluorene. Cancer Lett. 1995;95:39-47 pubmed
    ..No mutational hot regions were found in the lac gene...
  5. Pero R, Hagmar L, Seidegard J, Bellander T, Attewell R, Skerfving S. Biological effects in a chemical factory with mutagenic exposure. II. Analysis of unscheduled DNA synthesis and adenosine diphosphate ribosyl transferase, epoxide hydrolase, and glutathione transferase in resting mononuclear leukocytes. Int Arch Occup Environ Health. 1988;60:445-51 pubmed
    ..The exposure in this factory was complex, involving over 100 chemicals including several well known carcinogens. However, no apparent significant associations to exposure could be established...
  6. Mallamaci M, Bascoy M, Brown J, Combates N, Winkle S. Locating binding sites for the carcinogen N-acetoxy-N-acetyl-2-aminofluorene using restriction enzyme inhibition assays. J Biomol Struct Dyn. 1992;10:83-96 pubmed
    ..Comparison of the sequences at the sites of inhibition on the three DNAs indicates that all sites have common sequence elements: the presence of either the sequence T(C/G)TT(G/C) or the sequence T(G/C)CTT(G/C)...
  7. Kemp M, Lindsey Boltz L, Sancar A. The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by bulky adduct-containing DNA. J Biol Chem. 2011;286:19237-46 pubmed publisher
    ..Because the DNA damage response kinase ATM and Rad3-related (ATR) is also stimulated by bulky DNA adducts, we conclude that a common biochemical mechanism exists for activation of DNA-PK, ATM, and ATR by bulky adduct-containing DNA...
  8. Liao Q, Shen C, Vouros P. GenoMass--a computer software for automated identification of oligonucleotide DNA adducts from LC-MS analysis of DNA digests. J Mass Spectrom. 2009;44:549-60 pubmed publisher
    ..The software program potentially can be further expanded to postulate unknown DNA sequences and recognize the adduction sites...
  9. Said B, Ross M, Hamade A, Matsumoto D, Shank R. DNA-damaging effects of genotoxins in mixture: nonadditive effects of aflatoxin B1 and N-acetylaminofluorene on their mutagenicity in Salmonella typhimurium. Toxicol Sci. 1999;52:226-31 pubmed
    ..These results demonstrate effects, other than additive, of sequential exposures to two genotoxins on the induction of mutations in a bacterial system...

More Information

Publications62

  1. Mirkes P, Doggett B, Cornel L. Induction of a heat shock response (HSP 72) in rat embryos exposed to selected chemical teratogens. Teratology. 1994;49:135-42 pubmed
    ..Although only a small sample of chemical teratogens was studied, our results suggest that the heat shock response, characterized by the synthesis and accumulation of HSP 72, is not a general biomarker for chemical teratogens...
  2. Nairn R, Tang M, Wang R, Adair G, Humphrey R. Processing of 2-aminofluorene and 2-acetylaminofluorene DNA adducts in Chinese hamster ovary cells. Carcinogenesis. 1988;9:1369-75 pubmed
  3. Armier J, Mezzina M, Leng M, Fuchs R, Sarasin A. N-acetoxy-N-2-acetylaminofluorene-induced damage on SV40 DNA: inhibition of DNA replication and visualization of DNA lesions. Carcinogenesis. 1988;9:789-95 pubmed
    ..We therefore assume that AAF-adducts severely block the progression of the replication forks by inhibiting, at least, the in vivo polymerization of the leading strand...
  4. Combates N, Winkle S. Using lambda exonuclease inhibition assays to map carcinogen binding sites. J Biomol Struct Dyn. 1992;10:63-72 pubmed
    ..These carcinogen produced inhibition sites occur in sequences which are similar, suggesting that acetoxyAAF preferentially may target a small number of sequences...
  5. Van Sloun P, Varlet I, Sonneveld E, Boei J, Romeijn R, Eeken J, et al. Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage. Mol Cell Biol. 2002;22:2159-69 pubmed
    ..Together, these data are consistent with involvement of polymerase zeta in translesion synthesis of endogenously and exogenously induced DNA lesions...
  6. van Oosterwijk M, Filon R, Kalle W, Mullenders L, van Zeeland A. The sensitivity of human fibroblasts to N-acetoxy-2-acetylaminofluorene is determined by the extent of transcription-coupled repair, and/or their capability to counteract RNA synthesis inhibition. Nucleic Acids Res. 1996;24:4653-9 pubmed
    ..This indicates that the subset of lesions which are capable of stalling RNA polymerase II, and are, therefore, a substrate for TCR, are also the lesions which are very efficiently recognized by the global genome repair system...
  7. Olivero O, Semino C, Poirier M. Localization of DNA adducts induced by N-acetoxy-N-2-acetylaminofluorene in Chinese hamster ovary cells using electron microscopy and colloidal gold. Genes Chromosomes Cancer. 1990;2:130-6 pubmed
    ..15-26 in the surrounding cytoplasm. Treated cells incubated with normal rabbit serum or specific adduct-absorbed serum showed 19-34 particles for all cellular compartments...
  8. Kuo M, Liu Z, Wei Y, Lin Lee Y, Tatebe S, Mills G, et al. Induction of human MDR1 gene expression by 2-acetylaminofluorene is mediated by effectors of the phosphoinositide 3-kinase pathway that activate NF-kappaB signaling. Oncogene. 2002;21:1945-54 pubmed
    ..These results demonstrated that 2-AAF up-regulates MDR1 expression is mediated by the multiple effectors of the PI3K signaling pathway...
  9. Oh S, Kim K, Lee S, Yeh B. Identification of mutagenic site of c-H-ras oncogene damaged by N-acetoxyacetylaminofluorene(AAAF). Yonsei Med J. 1991;32:207-14 pubmed
    A molecularly cloned human cellular H-ras (c-H-ras) oncogene(pbc N1 plasmid) was treated with N-acetoxyacetylaminofluorene (AAAF) in vitro and subcloned into E.coli...
  10. Narachi M, Boyd J. The giant (gt) mutants of Drosophila melanogaster alter DNA metabolism. Mol Gen Genet. 1985;199:500-6 pubmed
    ..These findings strengthen the suggestion that the genetic instability associated with gt is related to perturbations in chromosome metabolism (Green 1982)...
  11. Olivero O, Huitfeldt H, Poirier M. Chromosome site-specific immunohistochemical detection of DNA adducts in N-acetoxy-2-acetylaminofluorene--exposed Chinese hamster ovary cells. Mol Carcinog. 1990;3:37-43 pubmed
    ..Thus, the stage of cell cycle in which adducts are induced is an important factor in the specific location of the highest concentrations of this type of DNA lesion...
  12. Fornace A, Alamo I, Hollander M. DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci U S A. 1988;85:8800-4 pubmed
    ..Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury...
  13. Black K, McFarland R, Grisham J, Smith G. S-phase block and cell death in human lymphoblasts exposed to benzo[a]pyrene diol epoxide or N-acetoxy-2-acetylaminofluorene. Toxicol Appl Pharmacol. 1989;97:463-72 pubmed
    ..However, additional processes, such as perturbation of transcription, may be involved in lethality after exposure to doses that immediately and completely inhibit population growth...
  14. Lund Pero M, Pero R, Miller D. The nonspecific esterases of human mononuclear leukocytes metabolize arylamine carcinogens and steroids esters. Eur J Haematol. 1989;43:158-66 pubmed
    ..e. as it may relate to immune function) and in the endogenous production of steroids from their naturally occurring esters emphasizes the importance of continuing their characterization...
  15. Strauss B, Wang J. Role of DNA polymerase 3'----5' exonuclease activity in the bypass of aminofluorene lesions in DNA. Carcinogenesis. 1990;11:2103-9 pubmed
  16. Jansen J, Olsen A, Wiger R, Naegeli H, de Boer P, van der Hoeven F, et al. Nucleotide excision repair in rat male germ cells: low level of repair in intact cells contrasts with high dual incision activity in vitro. Nucleic Acids Res. 2001;29:1791-800 pubmed
    ..We hypothesize that sequestering of NER proteins by mispaired regions in DNA involved in synapsis and recombination may underlie the lack of NER activity in premeiotic cells...
  17. Flarakos J, Xiong W, Glick J, Vouros P. A deoxynucleotide derivatization methodology for improving LC-ESI-MS detection. Anal Chem. 2005;77:2373-80 pubmed
    ..Our results demonstrate the utility of simple reactions for the enhanced detection of a mononucleotide in positive ion mode ESI MS and the application of this technique for the detection of dGp-DNA adducts at the low-femtomole level...
  18. Olsson I, Pero R, Olofsson T, Bryngelsson C. N-acetoxy-2-acetylaminofluorene induced unscheduled DNA synthesis of granulopoietic precursor cells in chronic myeloid leukemia. Carcinogenesis. 1980;1:547-52 pubmed
    ..Nevertheless these results are consistent with the hypothesis that increases in NA-AAF induced UDS signal the evolution during chronic phase CML of cell populations of increasing malignancy which escape growth control...
  19. Jansen L, Verhage R, Brouwer J. Preferential binding of yeast Rad4.Rad23 complex to damaged DNA. J Biol Chem. 1998;273:33111-4 pubmed
    ..These data suggest that Rad4.Rad23 interacts with DNA damage during NER and may play a role in recognition of the damage...
  20. Said B, Ross M, Salib T, Shank R. Modulation of DNA adduct formation by successive exposures of DNA to small and bulky chemical carcinogens. Carcinogenesis. 1995;16:3057-62 pubmed
  21. Spodheim Maurizot M, Saint Ruf G, Leng M. Antibodies to N-hydroxy-2-aminofluorene modified DNA as probes in the study of DNA reacted with derivatives of 2-acetylaminofluorene. Carcinogenesis. 1980;1:807-12 pubmed
    ..Moreover, the same sites seem to be reactive also in the direct reaction of N-AcO-AAF with dGMP. Circular dichroism measurements of modified DNA confirm the RIA results...
  22. Gichner T, Voutsinas G, Patrineli A, Kappas A, Plewa M. Antimutagenicity of three isomers of aminobenzoic acid in Salmonella typhimurium. Mutat Res. 1994;309:201-10 pubmed
    ..typhimurium strain YG1024. The aminobenzoic acid isomers exhibited no inhibitory effects towards the direct-acting agent 2-acetoxy-2-acetylaminofluorene, the stable diacetylated metabolic product of 2-AF...
  23. Smith B, Marsilio E. Methylation of the alpha 2(I) collagen gene in chemically transformed rat liver epithelial cells. Biochem J. 1988;253:269-73 pubmed
    ..Since inhibition of methylation by azacytidine induces transcription of the alpha 2(I) gene, DNA methylation of W8 alpha 2(I) promoter-5' region could contribute to altered collagen production in these cells...
  24. Thielmann H, Popanda O, Edler L, Jung E. Clinical symptoms and DNA repair characteristics of xeroderma pigmentosum patients from Germany. Cancer Res. 1991;51:3456-70 pubmed
    ..Weighted means of DNA repair synthesis of XP complementation groups, however, showed reductions hinting at impaired excision of distinct alkylated bases.(ABSTRACT TRUNCATED AT 400 WORDS)..
  25. Pero R, Johnson D, Markowitz M, Doyle G, Lund Pero M, Seidegard J, et al. DNA repair synthesis in individuals with and without a family history of cancer. Carcinogenesis. 1989;10:693-7 pubmed
  26. Carothers A, Urlaub G, Mucha J, Yuan W, Chasin L, Grunberger D. A mutational hot spot induced by N-hydroxy-aminofluorene in dihydrofolate reductase mutants of Chinese hamster ovary cells. Carcinogenesis. 1993;14:2181-4 pubmed
    ..These results are compared with our previous analyses of mutants induced with the related aromatic amine, N-2-acetoxy-2-acetyl-aminofluorene...
  27. Heflich R, Djuric Z, Zhuo Z, Fullerton N, Casciano D, Beland F. Metabolism of 2-acetylaminofluorene in the Chinese hamster ovary cell mutation assay. Environ Mol Mutagen. 1988;11:167-81 pubmed
    ..The limited O-acetylase activity in CHO cells appeared to contribute to the low sensitivity of these cells toward mutation induction by arylamines and arylamides...
  28. Ogawa H, Kimura H, Koya M, Higuchi H, Kato T. N-acetoxy-N-acetyl-2-aminofluorene-induced mutation spectrum in a human hprt cDNA shuttle vector integrated into mammalian cells. Carcinogenesis. 1993;14:2245-50 pubmed
    ..Implied significance of slippage--misalignment as a fundamental mechanism for mutagenesis is discussed...
  29. Tang M, Bohr V, Zhang X, Pierce J, Hanawalt P. Quantification of aminofluorene adduct formation and repair in defined DNA sequences in mammalian cells using the UVRABC nuclease. J Biol Chem. 1989;264:14455-62 pubmed
    ..This new technique has the potential to detect a variety of chemical carcinogen induced DNA adducts at the gene level in cultured cells and in DNA isolated from animal tissues...
  30. Tada M, Ikeda S, Suzuki M, Minoura Y, Kojima M, Morita T. Spectrophotometrical and immunochemical studies on the conformational changes in poly(dG-dC).poly(dG-dC) after modification by 4-hydroxyaminoquinoline 1-oxide. Biochim Biophys Acta. 1991;1090:29-37 pubmed
    ..poly(dG-dC) in Z-form conformation. These monoclonal antibodies may recognize a unique conformation in poly(dG-dC).poly(dG-dC) after 4HAQO modification...
  31. Lybak S, Pero R. The benzamide derivative metoclopramide causes DNA damage and inhibition of DNA repair in human peripheral mononuclear leukocytes at clinically relevant doses. Carcinogenesis. 1991;12:1613-7 pubmed
    ..The effect of MCA on DNA damage measured by nucleoid sedimentation has also been demonstrated in permeabilized cells. These data indicate that the DNA-damaging effect of MCA is not dependent on surface receptors or cytoplasmic processes...
  32. Popanda O, Thielmann H. Comparison of DNA-incising capacities in fibroblast strains from the Mannheim XP collection after treatment with N-acetoxy-2-acetylaminofluorene and UV light. J Cancer Res Clin Oncol. 1988;114:459-67 pubmed
    ..These data suggest that the sensitivity of XP cells towards UV light or (Ac)2ONFln is due to the same enzymatic defect, namely impaired incision of DNA containing pyrimidine dimers or (Ac)2ONFln-DNA adducts...
  33. Mahabir A, Schaap M, Pennings J, van Benthem J, Hendriksen C, van Steeg H. Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells. BMC Genomics. 2010;11:24 pubmed publisher
    ..Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls...
  34. Mirkes P, Little S, Beland F, Huitfeldt H, Poirier M. Quantitation and immunohistochemical localization of DNA adducts in rat embryos and associated yolk sac membranes exposed in vitro to N-acetoxy-2-acetylaminofluorene (N-Ac-AAF). Teratog Carcinog Mutagen. 1991;11:93-102 pubmed
    ..Our initial findings indicate that specific DNA adduct antibodies may be useful in the study of teratogenesis induced by a wide variety of agents that modify DNA...
  35. Weisenberger D, Romano L. Cytosine methylation in a CpG sequence leads to enhanced reactivity with Benzo[a]pyrene diol epoxide that correlates with a conformational change. J Biol Chem. 1999;274:23948-55 pubmed
  36. Riedinger K, Hanford M, Farber R. Induction of frameshift mutations in cultured mammalian cells within a transfected sequence containing a poly(dC-dA).poly(dT-dG) microsatellite. Environ Mol Mutagen. 1996;28:276-83 pubmed
    ..This system can be modified to include different short tandem repeat sequences as targets for testing of compounds that are suspected of having frameshift-inducing activities...
  37. McGregor W, Mah M, Chen R, Maher V, McCormick J. Lack of correlation between degree of interference with transcription and rate of strand specific repair in the HPRT gene of diploid human fibroblasts. J Biol Chem. 1995;270:27222-7 pubmed
    ..Therefore, the extent to which a particular lesion blocks transcription in vitro does not predict its rate of preferential or transcription-coupled excision repair...
  38. Stark K, Harris C, Juchau M. Influence of electrophilic character and glutathione depletion on chemical dysmorphogenesis in cultured rat embryos. Biochem Pharmacol. 1989;38:2685-92 pubmed
  39. Koffel Schwartz N, Fuchs R. Genetic control of AAF-induced mutagenesis at alternating GC sequences: an additional role for RecA. Mol Gen Genet. 1989;215:306-11 pubmed
    ..Therefore, RecA does not actively participate in the fixation of the mutation. A molecular model for this "additional" role of RecA is proposed...
  40. Narayanswami S, Hamkalo B. DNA sequence mapping using electron microscopy. Genet Anal Tech Appl. 1991;8:14-23 pubmed
    ..This technology is applicable both to TEM and SEM preparations of chromosomes, and we have used it to map a number of highly and moderately repeated sequences on whole mount metaphase chromosomes...
  41. Lanuszewska J, Widlak P. High mobility group 1 and 2 proteins bind preferentially to DNA that contains bulky adducts induced by benzo[a]pyrene diol epoxide and N-acetoxy-acetylaminofluorene. Cancer Lett. 2000;158:17-25 pubmed
    ..In contrast, DNA modified by dimethyl sulfate was not preferentially recognised by HMG-1/2...
  42. Sunesen M, Selzer R, Brosh R, Balajee A, Stevnsner T, Bohr V. Molecular characterization of an acidic region deletion mutant of Cockayne syndrome group B protein. Nucleic Acids Res. 2000;28:3151-9 pubmed
    ..Our data indicate that the highly acidic region of CSB is not essential for the TCR and general genome repair pathways of UV- and NA-AAF-induced DNA lesions...
  43. Van Gijssel H, Stenius U, Mulder G, Meerman J. Lack of p53 protein expression in preneoplastic rat hepatocytes in vitro after exposure to N-acetoxy-acetylaminofluorene, X-rays or a proteasome inhibitor. Eur J Cancer. 2000;36:106-12 pubmed
    ..Therefore, loss of p53 may favour clonal expansion of preneoplastic hepatocytes in the rat after administration of hepatocarcinogens or X-rays...
  44. Wagner E, Repetny K, Tan J, Gichner T, Plewa M. Mutagenic synergy between paraoxon and mammalian or plant-activated aromatic amines. Environ Mol Mutagen. 1997;30:312-20 pubmed
    ..a mutagenic synergy with paraoxon and plant-activated m-phenylenediamine or with direct-acting 2-acetoxyacetylaminofluorene in Salmonella typhimurium cells [Gichner T et al. (1996): Environ Mol Mutagen 27; 59-66]...
  45. Mallamaci M, Reed D, Winkle S. Restriction enzyme mapping of carcinogen binding regions on pBR322. J Biomol Struct Dyn. 1992;10:73-82 pubmed
    ..The locations of the bands containing the acetoxyAAF for each enzyme overlap--suggesting that there are regions on pBR 322 which contain high affinity sites for acetoxyAAF binding...
  46. Wagner E, McMillan S, Plewa M. Cytotoxicity of organophosphorus ester (OP) insecticides and cytotoxic synergism of 2-acetoxyacetylaminofluorene (2AAAF) in Chinese hamster ovary (CHO) cells. Bull Environ Contam Toxicol. 2005;75:329-34 pubmed
  47. Maher V, Yang J, Mah M, McCormick J. Comparing the frequency and spectra of mutations induced when an SV-40 based shuttle vector containing covalently bound residues of structurally-related carcinogens replicates in human cells. Mutat Res. 1989;220:83-92 pubmed
    ..abstract truncated at 400 words)..
  48. Gerlach V, Feaver W, Fischhaber P, Friedberg E. Purification and characterization of pol kappa, a DNA polymerase encoded by the human DINB1 gene. J Biol Chem. 2001;276:92-8 pubmed
  49. Pero R, Anderson M, Doyle G, Anna C, Romagna F, Markowitz M, et al. Oxidative stress induces DNA damage and inhibits the repair of DNA lesions induced by N-acetoxy-2-acetylaminofluorene in human peripheral mononuclear leukocytes. Cancer Res. 1990;50:4619-25 pubmed
    ..Both ADP ribosylation and N-acetoxy-2-acetylaminofluorene-induced UDS were shown to be up- and down-regulated by the redox state of human mononuclear leukocytes indicating a unique mechanism of cellular control over DNA repair...
  50. Thayer J, Mirkes P. Programmed cell death and N-acetoxy-2-acetylaminofluorene-induced apoptosis in the rat embryo. Teratology. 1995;51:418-29 pubmed
    ..Because apoptosis also occurs in developmental cell death, it is possible that apoptosis induced by N-Ac-AAF is due to an alteration in cell fate via premature or ectopic induction of the cell death program...
  51. Mah M, Maher V, Thomas H, Reid T, King C, McCormick J. Mutations induced by aminofluorene-DNA adducts during replication in human cells. Carcinogenesis. 1989;10:2321-8 pubmed
    ..The most prominent mutation hot spot was also the most prominent hot spot for adduct formation as judged by the frequency of termination of in vitro polymerization by the Klenow fragment on N-AcO-TFA-AF-treated plasmids...
  52. Mao B, Gorin A, Gu Z, Hingerty B, Broyde S, Patel D. Solution structure of the aminofluorene-intercalated conformer of the syn [AF]-C8-dG adduct opposite a--2 deletion site in the NarI hot spot sequence context. Biochemistry. 1997;36:14479-90 pubmed
  53. Bhattacharyya N, Maher V, McCormick J. Ability of structurally related polycyclic aromatic carcinogens to induce homologous recombination between duplicated chromosomal sequences in mouse L cells. Mutat Res. 1989;211:205-14 pubmed
    ..In the rest, only a single copy of the Htk gene remained, reflecting a single reciprocal exchange within a chromatid or a single unequal exchange between sister chromatids...