hydroxyacetylaminofluorene

Summary

Summary: A N-hydroxylated derivative of 2-ACETYLAMINOFLUORENE that has demonstrated carcinogenic action.

Top Publications

  1. van de Poll M, van der Hulst D, Tates A, Meerman J. Correlation between clastogenicity and promotion activity in liver carcinogenesis by N-hydroxy-2-acetylaminofluorene, N-hydroxy-4'-fluoro-4-acetylaminobiphenyl and N-hydroxy-4-acetylaminobiphenyl. Carcinogenesis. 1990;11:333-9 pubmed
    ..Possibly, N-acetylated adducts to C8 of deoxyguanosine are involved in both clastogenicity and promotion...
  2. Sticha K, Bergstrom C, Wagner C, Hanna P. Characterization of hamster recombinant monomorphic and polymorphic arylamine N-acetyltransferases: bioactivation and mechanism-based inactivation studies with N-hydroxy-2-acetylaminofluorene. Biochem Pharmacol. 1998;56:47-59 pubmed
    ..The combined results indicate that the recombinant enzymes are catalytically and functionally identical to hamster NATs and, therefore, will be a useful resource for studies requiring purified NATs...
  3. Liu L, Wagner C, Hanna P. Isoform-selective inactivation of human arylamine N-acetyltransferases by reactive metabolites of carcinogenic arylamines. Chem Res Toxicol. 2009;22:1962-74 pubmed publisher
  4. Babson J, Gavitt N, Boteju L, Hanna P. Comparative toxicity and mutagenicity of N-hydroxy-2-acetylaminofluorene and 7-acetyl-N-hydroxy-2-acetylaminofluorene in human lymphoblasts. Mutat Res. 1992;269:73-8 pubmed
    ..In addition, the presence of electron-withdrawing 7-acetyl substituent that is thought to stabilize N-acetoxy intermediates, appears to enhance the biological activity of the unsubstituted N-OH-AAF...
  5. Sawada N, Ishikawa T. Reduction of potential for replicative but not unscheduled DNA synthesis in hepatocytes isolated from aged as compared to young rats. Cancer Res. 1988;48:1618-22 pubmed
    ..Thus, while the results suggest that potential for DNA replication markedly diminishes with age, DNA repair systems are well preserved...
  6. Meerman J, Tijdens R, Mulder G. The binding of reactive metabolites of the carcinogen N-hydroxy-2-acetylaminofluorene to DNA and protein in isolated rat liver nuclei: effects of glutathione and methionine. J Biochem Toxicol. 1986;1:1-10 pubmed
    ..However, such nucleophiles seem not to be effective with N-hydroxylamines, such as N-hydroxy-2-aminofluorene, formed by deacetylation of N-hydroxy-2-acetylaminofluorene...
  7. Meinl W, Meerman J, Glatt H. Differential activation of promutagens by alloenzymes of human sulfotransferase 1A2 expressed in Salmonella typhimurium. Pharmacogenetics. 2002;12:677-89 pubmed
  8. Ringer D, Howell B, Norton T, Woulfe G, Duffel M, Kosanke S. Evidence of two separate mechanisms for the decrease in aryl sulfotransferase activity in rat liver during early stages of 2-acetylaminofluorene-induced hepatocarcinogenesis. Mol Carcinog. 1994;9:2-9 pubmed
    ..These patterns may correspond, respectively, to cytotoxic and genotoxic mechanisms of 2AAF action...
  9. Nagata K, Ozawa S, Miyata M, Shimada M, Gong D, Yamazoe Y, et al. Isolation and expression of a cDNA encoding a male-specific rat sulfotransferase that catalyzes activation of N-hydroxy-2-acetylaminofluorene. J Biol Chem. 1993;268:24720-5 pubmed
    ..These data clearly indicate that ST1C1 cDNA codes a new form of a male-dominant sulfotransferase (HAST) responsible for the bioactivation of N-hydroxyarylamines in rat livers...

More Information

Publications62

  1. Fretland A, Doll M, Gray K, Feng Y, Hein D. Cloning, sequencing, and recombinant expression of NAT1, NAT2, and NAT3 derived from the C3H/HeJ (rapid) and A/HeJ (slow) acetylator inbred mouse: functional characterization of the activation and deactivation of aromatic amine carcinogens. Toxicol Appl Pharmacol. 1997;142:360-6 pubmed
    ..These studies demonstrate metabolic activation and deactivation by recombinant mouse NAT1, NAT2, and NAT3 proteins and confirm and extend previous studies on the molecular basis for the acetylation polymorphism in the mouse...
  2. Frijhoff A, Krul C, de Vries A, Kelders M, Weeda G, van Steeg H, et al. Influence of nucleotide excision repair on N-hydroxy-2-acetylaminofluorene-induced mutagenesis studied in lambda lacZ-transgenic mice. Environ Mol Mutagen. 1998;31:41-7 pubmed
    ..This study with XPA-/- lambda lacZ-transgenic mice shows that one of the components of NER, that is, the XPA protein, suppresses mutagenesis in vivo...
  3. Mangold B, Erickson J, Lohr C, McCann D, Mangold J. Self-catalyzed irreversible inactivation of rat hepatic aryl sulfotransferase IV by N-hydroxy-2-acetylaminofluorene. Carcinogenesis. 1990;11:1563-7 pubmed
    ..Furthermore, the results of the present study indicate that the previously reported in vivo decline in rat hepatic aryl sulfotransferase activity may be attributable in part to enzyme inactivation by its own reactive product...
  4. McKinzie P, Delongchamp R, Chen T, Parsons B. ACB-PCR measurement of K-ras codon 12 mutant fractions in livers of Big Blue rats treated with N-hydroxy-2-acetylaminofluorene. Mutagenesis. 2006;21:391-7 pubmed
    ..This data raises the possibility that N-OH-AAF may not only induce mutations by a genotoxic mechanism, but also by amplification of both de novo and pre-existing K-ras mutation...
  5. Malejka Giganti D, Ritter C, Decker R. Activation of the carcinogen N-hydroxy-N-(2-fluorenyl)benzamide via chemical and enzymatic oxidations. Comparison to oxidations of the structural analogue N-hydroxy-N-(2-fluorenyl)acetamide. Chem Res Toxicol. 1992;5:520-7 pubmed
    ..abstract truncated at 250 words)..
  6. Gilissen R, Meerman J. Bioactivation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene by sulfation in the rat liver changes during the cell cycle. Life Sci. 1992;51:1255-60 pubmed
    ..The relevance of the finding is discussed in relation to the resistance of proliferating (pre)neoplastic hepatocytes to the toxic and mitoinhibitory effects of N-hydroxy-2-acetylaminofluorene...
  7. Manam S, Shinder G, Joslyn D, Kraynak A, Hammermeister C, Leander K, et al. Dose-related changes in the profile of ras mutations in chemically induced CD-1 mouse liver tumors. Carcinogenesis. 1995;16:1113-9 pubmed
    ..Our results demonstrate that the dosing procedure can materially affect the pattern of ras gene mutation in mouse liver tumors...
  8. Lewis A, Otake Y, Walle U, Walle T. Sulphonation of N-hydroxy-2-acetylaminofluorene by human dehydroepiandrosterone sulphotransferase. Xenobiotica. 2000;30:253-61 pubmed
    ..5. This is the first paper to demonstrate the involvement of the human DHEA-ST in the sulphonation of an N-hydroxylated aromatic amide carcinogen...
  9. 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...
  10. Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer D, Takami Y, Nakayama T, et al. Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem. 1998;273:33929-35 pubmed
    ..The results provide a foundation for the investigation into the functional relevance of these new SULT1C sulfotransferases in different human tissues/organs...
  11. Yueh M, Nguyen N, Famourzadeh M, Strassburg C, Oda Y, Guengerich F, et al. The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines. Carcinogenesis. 2001;22:943-50 pubmed
    ..The results also indicate that while a potential toxicant such as N-hydroxy-PhIP can serve as substrate for glucuronidation, its biological actions can exceed the capacity of the detoxification pathway to prevent the mutagenic episode...
  12. Nagelkerke J, de Bont A, de Bont H, Tijdens I, Mulder G, Meerman J. Fasting increases the susceptibility of rat hepatocytes to the cytotoxic effects of N-hydroxy-acetylaminofluorene. Effects on mitochondrial respiration and membrane potential. Biochem Pharmacol. 1992;44:2339-45 pubmed
  13. Yoshinari K, Nagata K, Shimada M, Yamazoe Y. Molecular characterization of ST1C1-related human sulfotransferase. Carcinogenesis. 1998;19:951-3 pubmed
    ..These results suggest that human ST1C2 has a clear different substrate specificity, in spite of the structural similarity, with rat ST1C1...
  14. Kolanczyk R, Rutks I, Gutmann H. The catalytic effect of bovine serum albumin on the ortho rearrangement of the potential ultimate carcinogen, N-(sulfooxy)-2-(acetylamino)fluorene, generated enzymatically from N-hydroxy-2-(acetylamino)fluorene and evidence for substrate specificity . Chem Res Toxicol. 1991;4:187-94 pubmed
    ..abstract truncated at 250 words)..
  15. Kitamura S, Takekawa K, Sugihara K, Tatsumi K, Ohta S. Pseudoenzymatic reduction of N-hydroxy-2-acetylaminofluorene to 2-acetylaminofluorene mediated by cytochrome P450. Carcinogenesis. 1999;20:347-50 pubmed
    ..The microsomal reduction of N-OH-AAF appears to be a non-enzymatic reaction by the reduced flavin, catalyzed by the heme group of cytochrome P450...
  16. Chen T, Mittelstaedt R, Aidoo A, Hamilton L, Beland F, Casciano D, et al. Comparison of hprt and lacI mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminofluorene-treated Big Blue rats. Environ Mol Mutagen. 2001;37:195-202 pubmed
    ..The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat. Environ. Mol. Mutagen. 37:195-202, 2001. Published 2001 Wiley-Liss, Inc...
  17. Malejka Giganti D, Magat W, Decker R. Sex hormone-mediated effects on the phase I and phase II metabolism of N-2-fluorenylacetamide. Modulation of 9-hydroxylation. Biochem Pharmacol. 1989;38:1075-82 pubmed
    ..Hence, in the presence of male hormones, relatively large amounts of 9-OH-2-FAA were formed and possibly retained in the liver. A role of this alcohol as a potential promoter in hepatocarcinogenesis by 2-FAA is suggested...
  18. Harris C, Stark K, Juchau M. Glutathione status and the incidence of neural tube defects elicited by direct acting teratogens in vitro. Teratology. 1988;37:577-90 pubmed
  19. Wick M, Jantan I, Hanna P. Irreversible inhibition of rat hepatic transacetylase activity by N-arylhydroxamic acids. Biochem Pharmacol. 1988;37:1225-31 pubmed
    ..The results of this study indicate that N-OH-AAF and N-OH-AAC have potential for use as tools in the investigation of rat hepatic transacetylases...
  20. Holme J, Søderlund E. Modulation of genotoxic and cytotoxic effects of aromatic amines in monolayers of rat hepatocytes. Cell Biol Toxicol. 1984;1:95-110 pubmed
  21. Ritter C, Malejka Giganti D. Oxidations of the carcinogen N-hydroxy-N-(2-fluorenyl)acetamide by enzymatically or chemically generated oxidants of chloride and bromide. Chem Res Toxicol. 1989;2:325-33 pubmed
    ..With time N-chlorotaurine and N-bromotaurine appeared to undergo a pH-dependent halide exchange with Br- and Cl-, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)..
  22. Ferguson R, Doll M, Rustan T, Baumstark B, Hein D. Syrian hamster monomorphic N-acetyltransferase (NAT1) alleles: amplification, cloning, sequencing, and expression in E. coli. Pharmacogenetics. 1994;4:82-90 pubmed
    ..Also, the over-expressed NAT1 proteins displayed substrate-specificity and electrophoretic mobilities characteristic of NAT1 isolated from Syrian hamster liver and colon cytosols...
  23. Ledwith B, Joslyn D, Troilo P, Leander K, Clair J, Soper K, et al. Induction of minisatellite DNA rearrangements by genotoxic carcinogens in mouse liver tumors. Carcinogenesis. 1995;16:1167-72 pubmed
    ..Our results suggest that DNA fingerprinting may be a valuable assay for differentiating certain chemically induced tumors from spontaneous tumors...
  24. Kolanczyk R, Gutmann H, Rutks I. Effect of bovine serum albumin on the extent of ortho rearrangement of N-(sulfooxy)-2-fluorenylacetamide and of enzymatically activated N-hydroxy-2-fluorenylacetamide and on the binding of reactive esters to nucleic acids. Chem Res Toxicol. 1992;5:274-9 pubmed
    ..The data support the view that the reactive electrophile is N-acetoxy-2-fluorenamine, resulting from the N,O-transacetylation of N-hydroxy-2-fluorenylacetamide.(ABSTRACT TRUNCATED AT 250 WORDS)..
  25. Hoffmann G, Janel Bintz R, Fuchs R. Induction of -2 frameshift mutations by 2-nitrofluorene, N-hydroxyacetylaminofluorene, and N-2-acetylaminofluorene in reversion assays in Escherichia coli strains differing in permeability and acetyltransferase activity. Mutat Res. 2001;493:127-37 pubmed
    The mutagenicity of 2-nitrofluorene (NF), N-hydroxyacetylaminofluorene (N-OH-AAF), and N-2-acetylaminofluorene (AAF) was measured in strains of Escherichia coli that contain a lacZ allele that reverts by -2 frameshift mutations from CG(5) ..
  26. Santoni Rugiu E, Silverman J. Functional characterization of the rat mdr1b encoded P-glycoprotein: not all inducing agents are substrates. Carcinogenesis. 1997;18:2255-63 pubmed
    ..The fact that compounds which are not themselves substrates can induce P-glycoprotein expression may have implications for pharmacokinetic interactions and chemotherapy...
  27. Herrera G, Urios A, Aleixandre V, Blanco M. Mutability by polycyclic hydrocarbons is improved in derivatives of Escherichia coli WP2 uvrA with increased permeability. Mutat Res. 1993;301:1-5 pubmed
    ..The new permeable strains, when tested for mutagenesis induced by polycyclic hydrocarbons, showed a mutagenic response higher than that of the parental strains...
  28. Tamura H, Harada Y, Miyawaki A, Mikoshiba K, Matsui M. Molecular cloning and expression of a cDNA encoding an olfactory-specific mouse phenol sulphotransferase. Biochem J. 1998;331 ( Pt 3):953-8 pubmed
  29. Van Gijssel H, Maassen C, Mulder G, Meerman J. p53 protein expression by hepatocarcinogens in the rat liver and its potential role in mitoinhibition of normal hepatocytes as a mechanism of hepatic tumour promotion. Carcinogenesis. 1997;18:1027-33 pubmed
    ..Because this is not observed with non-hepatocarcinogenic analogues, it suggests an involvement of p53 expression in hepatic tumour promotion. A possible mechanism is discussed...
  30. Cheo D, Friedberg E. Use of nucleotide excision repair-deficient mice as a model for chemically induced lung cancer. Methods Mol Med. 2003;74:481-91 pubmed
  31. Nohmi T, Yamada M, Matsui M, Matsui K, Watanabe M, Sofuni T. Involvement of umuDCST genes in nitropyrene-induced -CG frameshift mutagenesis at the repetitive CG sequence in the hisD3052 allele of Salmonella typhimurium. Mol Gen Genet. 1995;247:7-16 pubmed
    ..reversion rate induced by 1-NP or 1,8-DNP, but it did not affect reversion induced by 2-NF, Glu-P-1 or N-hydroxyacetylaminofluorene (N-OH-AAF)...
  32. Monteith D. Inhibition of sulfotransferase in primary cultures of human hepatocytes affecting metabolism and binding of 2-acetylaminofluorene. Cancer Lett. 1992;64:109-15 pubmed
    ..Therefore, PCP may inhibit a detoxication pathway. This study supports N,O-acyltransferase as the critical enzyme for the formation of the major reactive metabolite in human liver...
  33. Moyer G, Gumbiner B, Austin G. Binding of N-hydroxy acetylaminofluorene to eu- and heterochromatin fractions of rat liver in vivo. Cancer Lett. 1977;2:259-65 pubmed
    ..However, the bound carcinogen appeared to be eliminated more rapidly from euchromatin than from heterochromatin by DNA repair processes...
  34. van de Poll M, van der Hulst D, Tates A, Mulder G, Meerman J. The role of specific DNA adducts in the induction of micronuclei by N-hydroxy-2-acetylaminofluorene in rat liver in vivo. Carcinogenesis. 1989;10:717-22 pubmed
    ..e. N-deoxyguanosin-8-yl-AAF and/or 3-deoxyguanosin-N2-yl-AAF) and is not related to the formation of the deacetylated DNA adduct N-deoxyguanosin-8-yl-AF...
  35. King C, Olive C, Cardona R. Activation of carcinogenic arylhydroxamic acids by human tissues. J Natl Cancer Inst. 1975;55:285-7 pubmed
    ..The unstable N-acetoxyarylamines formed by these enzymes reacted spontaneously with the tRNA to give covalently linked adducts with the nucleic acid...
  36. Hein D, Doll M, Gray K, Rustan T, Ferguson R. Metabolic activation of N-hydroxy-2-aminofluorene and N-hydroxy-2-acetylaminofluorene by monomorphic N-acetyltransferase (NAT1) and polymorphic N-acetyltransferase (NAT2) in colon cytosols of Syrian hamsters congenic at the NAT2 locus. Cancer Res. 1993;53:509-14 pubmed
  37. Meerman J, Ringer D, Coughtrie M, Bamforth K, Gilissen R. Sulfation of carcinogenic aromatic hydroxylamines and hydroxamic acids by rat and human sulfotransferases: substrate specificity, developmental aspects and sex differences. Chem Biol Interact. 1994;92:321-8 pubmed
    ..Sulfation activity towards these compounds was also found in fetal and neonatal liver and adrenals. These compounds probably are sulfated by several different sulfotransferases in humans...
  38. Lim L, Corbett B, Corbett M. Irreversible inhibition of the cytosolic metabolism of N-hydroxy-2-acetylaminofluorene by its glycolyl analog. Cancer Lett. 1987;37:205-11 pubmed
    ..In contrast, both the glycolyl and acetyl hydroxamic acid derivatives were metabolized to a similar extent by enzymes in the microsomal fraction...
  39. Holmes T, Rainsford K. Differential effects of non-genotoxic carcinogens and proliferating agents on cell growth, survival and apoptosis in hepatic cells in vitro. Life Sci. 2001;69:2975-92 pubmed
    ..The results emphasize the importance of considering necrotic reactions from effects on apoptosis in detecting non-genotoxic carcinogens...
  40. Chipman J, Davies J. Reduction of 2-acetylaminofluorene-induced unscheduled DNA synthesis in human and rat hepatocytes by butylated hydroxytoluene. Mutat Res. 1988;207:193-8 pubmed
    ..This effect contracts with a BHT-mediated increase in the efflux of 2AAF-derived mutagens from liver cells which may contribute to enhanced extrahepatic carcinogenesis...
  41. Wick M, Hanna P. Bioactivation of N-arylhydroxamic acids by rat hepatic N-acetyltransferase. Detection of multiple enzyme forms by mechanism-based inactivation. Biochem Pharmacol. 1990;39:991-1003 pubmed
  42. Okinaka R, Whaley T, Strniste G. Differential effects induced by N-hydroxy-2-acetylaminofluorene and N-hydroxy-2-aminofluorene in DNA excision-repair-deficient Chinese hamster cells. Mutat Res. 1988;209:45-50 pubmed
    ..1977) suggest that the minor DNA adduct species, N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene, may be responsible for the hypermutagenicity witnessed in DNA excision-repair-deficient cells treated with N-OH-AAF...
  43. Wang C, Imaida K, Zukowski K, Lee M. Lack of carcinogenicity of 2-aminofluorene, its glucuronide and the glucuronide of N-hydroxy-2-acetylaminofluorene in heterotopic bladder of the rat. Cancer Lett. 1991;56:153-7 pubmed
    ..These results are consistent with the hypothesis that the N-glucuronides of hydroxylamines, but not the O-glucuronides of hydroxamic acids, are responsible for bladder carcinogenesis by arylamines...
  44. Kroese E, Bannenberg G, Dogterom P, Noach A, Nagelkerke J, Meerman J. Lipid peroxidation and protein thiol depletion are not involved in the cytotoxicity of N-hydroxy-2-acetylaminofluorene in isolated rat hepatocytes. Biochem Pharmacol. 1990;40:1885-92 pubmed
    ..It is concluded, therefore, that neither lipid peroxidation nor depletion of protein thiols, but possibly loss of intracellular ATP, is involved in the sulfation-dependent cytotoxic mechanism of N-OH-AAF in isolated rat hepatocytes...
  45. Chen T, Mittelstaedt R, Shelton S, Dass S, Manjanatha M, Casciano D, et al. Gene- and tissue-specificity of mutation in Big Blue rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene. Environ Mol Mutagen. 2001;37:203-14 pubmed
    ..The tissue-specificity of the mutation spectra may contribute to targeting tumor formation to the liver. Environ. Mol. Mutagen. 37:203-214, 2001. Published 2001 Wiley-Liss, Inc...
  46. Harris C, Stark K, Luchtel D, Juchau M. Abnormal neurulation induced by 7-hydroxy-2-acetylaminofluorene and acetaminophen: evidence for catechol metabolites as proximate dysmorphogens. Toxicol Appl Pharmacol. 1989;101:432-46 pubmed
  47. Ritter C, Malejka Giganti D. Activation of the carcinogens N-hydroxy-N-2-fluorenylbenzamide and N-hydroxy-N-2-fluorenylacetamide via deacylations and acetyl transfers by rat peritoneal serosa and liver. Carcinogenesis. 1994;15:163-70 pubmed
    ..The study provides first evidence for activation of N-OH-2-FBA by rat liver and of both compounds by peritoneum in vitro...
  48. Kiehlbauch C, Lam Y, Ringer D. Homodimeric and heterodimeric aryl sulfotransferases catalyze the sulfuric acid esterification of N-hydroxy-2-acetylaminofluorene. J Biol Chem. 1995;270:18941-7 pubmed
  49. Klöhn P, Neumann H. Impairment of respiration and oxidative phosphorylation by redox cyclers 2-nitrosofluorene and menadione. Chem Biol Interact. 1997;106:15-28 pubmed
    ..The results support the notion that redox cyclers impair oxidative phosphorylation by establishing alternative pathways for electron transport in the respiratory chain...
  50. Vijayaraghavan P, Malejka Giganti D. Modulations of hepatic gamma-glutamyltranspeptidase and N-hydroxy-N-2-fluorenylacetamide sulfotransferase activities following treatment of rats with a hepatocarcinogenic regimen: effect of partial hepatectomy. Environ Health Perspect. 1994;102 Suppl 6:105-8 pubmed
    ..5%). After 31, 66, and 87 days, the respective decreases of 27, 29, and 41% in the +PH group were significant.(ABSTRACT TRUNCATED AT 250 WORDS)..
  51. Corbett M, Lim L, Corbett B, Johnston J, Wiebkin P. Covalent binding of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-glycolyl-2-aminofluorene to rat hepatocyte DNA: in vitro and cell-suspension studies. Chem Res Toxicol. 1988;1:41-6 pubmed
    ..The microsomal fraction catalyzed the binding of N-OH-GAF to DNA at a rate that was about twice that observed for N-OH-AAF.(ABSTRACT TRUNCATED AT 250 WORDS)..
  52. Lai C, Miller E, Miller J, Liem A. The essential role of microsomal deacetylase activity in the metabolic activation, DNA-(deoxyguanosin-8-yl)-2-aminofluorene adduct formation and initiation of liver tumors by N-hydroxy-2-acetylaminofluorene in the livers of infant male B6C3F1 mice. Carcinogenesis. 1988;9:1295-302 pubmed
    ..It is concluded that deacetylation of N-hydroxy-AAF to N-hydroxy-AF is essential for the metabolic activation, DNA-N-(dGuo-8-yl)-AF adduct formation and liver tumor initiation in infant male B6C3F1 mice by N-hydroxy-AAF...
  53. Boteju L, Hanna P. Bioactivation of N-hydroxy-2-acetylaminofluorenes by N,O-acyltransferase: substituent effects on covalent binding to DNA. Carcinogenesis. 1993;14:1651-7 pubmed
    ..It is proposed that a nitrene intermediate is involved in the formation of covalent adducts with DNA when 7-Ac-N-OH-AAF is activated by N,O-acyltransfer...