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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Mar;86(3):264–269. doi: 10.1111/j.1349-7006.1995.tb03049.x

Formation of 2‐Amino‐3‐methylimidazo[4,5‐f]quinoline‐ and 2‐Amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline‐sulfamates by cDNA‐expressed Mammalian Phenol Sulfotransferases

Shogo Ozawa 1,✉, Kiyoshi Nagata 1,†, Yasushi Yamazoe 1,†, Ryuichi Kato 1
PMCID: PMC5920814  PMID: 7744696

Abstract

In rat liver cytosol systems, 2‐amino‐3‐methylimidazo[4,5‐f]quinoIine (IQ) and 2‐amino‐3,8‐dimethyl‐imidazo[4,5‐f]quinoxaline (MelQx) were converted into their sulfamates in the presence of 3′‐phosphoadenosine 5′‐phosphosulfate at rates of 51.2 and 50.7 pmol/min/mg cytosol in the male, and 23.7 and 22.5 pmol/min/mg cytosol in the female, respectively. IQ‐sulfamate formation was low (0.24 pmol/min/mg cytosol) in human liver cytosols, and MeIQx‐sulfamate was not detected (<0.1 pmol/ min/mg cytosol). These results suggest only a minor contribution of IQ‐ and MeIQx‐sulfamate formation to the detoxification of both heterocyclic amines in humans. Using sulfotransferase cDNA‐expression systems, a rat ST1A1 arylsulfotransferase has been shown to catalyze the formation of the sulfamates, suggesting a role of the ST1A type of sulfotransferase in the N‐sulfation of heterocyclic amines.

Keywords: Pyrolysate carcinogen, Sulfation, N‐Sulfation, Sulfotransferase, cDNA expression

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REFERENCES

  • 1).Jakoby , W. B. , Sekura , R. D. , Lyon , E. S. , Marcus , C. J. and Wang , J.In , “ Enzymatic Basis of Detoxication ”. ed Jakoby W. B. , Vol.2 , pp . 199 – 228 ( 1980. ). Academic Press; , New York . [Google Scholar]
  • 2).Mulder , G. J.Sulfation—metabolic aspects . Prog. Drug Metab. , 8 , 35 – 100 ( 1984. ). [Google Scholar]
  • 3).Sugimura , T.New environmental carcinogens in daily life . Trends Pharmacol. Sci. , 9 , 205 – 209 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 4).Turesky , R. J. , Skipper , P. L. , Tannenbaum , S. R. , Coles , B. and Ketterer , B.Sulfamate formation is a major route for detoxication of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in the rat . Carcinogenesis , 7 , 1483 – 1485 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 5).Turesky , R. J. , Aeschbacher , H. U. , Wérzner , H. P. , Skipper , P. L. and Tannenbaum , S. R.Major routes of metabolism of the food‐borne carcinogen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline in the rat . Carcinogenesis , 9 , 1043 – 1048 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 6).Yamazoe , Y. , Nagata , K. , Ozawa , S. and Kato , R.Structural similarity and diversity of sulfotransferases . Chem.-Biol. Interact. , 92 , 107 – 117 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 7).Rich , K. J. , Murray , B. P. , Lewis , I , Rendell , N. B. , Davies , D. S. , Gooderham , N. J. and Boobis , A. R.N‐Hydroxy‐MeIQx is the major microsomal oxidation product of the dietary carcinogen MeIQx with human liver . Carcinogenesis , 13 , 2221 – 2226 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 8).Ozawa , S. , Nagata , K. , Gong , D. W. , Yamazoe , Y. and Kato , R.Nucleotide sequence of a full‐length cDNA (PST‐1) for aryl sulfotransferase from rat liver . Nucleic Acids Res. , 18 , 4001 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9).Ozawa , S. , Nagata , K. , Gong , D.‐W. , Yamazoe , Y. and Kato , R.Expression and functional characterization of a rat sulfotransferase (ST1A1) cDNA for sulfations of phenolic substrates in COS‐1 cells . Jpn. J. Pharmacol. , 61 , 153 – 156 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 10).Nagata , K. , Ozawa , S. , Miyata , M. , Shimada , M. , Gong , D.‐W. , Yamazoe , Y. and Kato , R.Isolation and expression of a cDNA encoding a male‐specific rat sulfotransferase that catalyzes activation of N‐hydroxy‐2‐acetyl‐aminofluorene . J. Biol. Chem. , 268 , 24720 – 24725 ( 1993. ). [PubMed] [Google Scholar]
  • 11).Yasumori , T. , Nagata , K. , Yang , S. K. , Chen , L.‐S. , Murayama , N. , Yamazoe , Y. and Kato , R.Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N‐demethylation in concentration‐dependent manner . Pharmacogenetics , 3 , 291 – 301 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 12).Ozawa , S. , Nagata , K. , Shimada , M. , Ueda , M. , Tsuzuki , T. , Yamazoe , Y. and Kato , R.Primary structures and properties of two related forms of aryl sulfotransferases in human liver . Pharmacogenetics , in press . [DOI] [PubMed]
  • 13).Abu‐Zeid , M. , Yamazoe , Y. and Kato , R.Sulfotransferase‐mediated DNA binding of N‐hydroxyarylamines (amide) in liver cytosols from human and experimental animals . Carcinogenesis , 13 , 1307 – 1314 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 14).Ozawa , S. , Chou , H.‐C. , Kadlubar , F. F. , Nagata , K. , Yamazoe , Y. and Kato , R.Activation of 2‐hydroxyamino‐1‐methyl‐6‐phenylimidazo [4,5‐b]pyridine by cDNA‐expressed human and rat arylsulfotransferases . Jpn. J. Cancer Res. , 85 , 1220 – 1228 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15).Turesky , R. J. , Bracco‐Hammer , I. , Markovic , J. , Richli , U. , Kappeler , A.‐M. and Welti , D. H.The contribution of N‐oxidation to the metabolism of the food‐borne carcinogen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline in rat hepatocytes . Chem. Res. Toxicol. , 3 , 524 – 535 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 16).Snyderwine , E. G. , Welti , D. H. , Fay , L. B. , Würzner , H. P. and Turesky , R. J.Metabolism of the food mutagen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in nonhuman primates undergoing carcinogen bioassay . Chem. Res. Toxicol. , 5 , 843 – 851 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 17).Inamasu , T. , Luks , H. , Vavrek , M. T. and Weisburger , J. H.Metabolism of 2‐amino‐3‐methylimidazo[4,5‐f]‐quinoline in the male rat . Food Chem. Toxicol. , 27 , 369 – 376 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 18).Vavrek , M. T. , Sidoti , P. , Reinhardt , J. and Weisburger , J. H.Effect of enzyme inducers on the metabolism of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) in the rat . Cancer Lett. , 48 , 183 – 188 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 19).Hein , D. W.Acetylator genotype and arylamine‐induced carcinogenesis . Biochim. Biophys. Acta , 948 , 37 – 66 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 20).Ozawa , S.Abu‐Zeid , M. , Kawakubo , Y. , Toyama , S. , Yamazoe , Y. and Kato , R.Monomorphic and polymorphic isozymes of arylamine N‐acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N‐acetylation polymorphism . Carcinogenesis , 11 , 2137 – 2144 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21).Hein , D. W. , Doll , M. A. , Rustan , T. D. , Gray , K. , Feng , Y. , Ferguson , R. J. and Grant , D. M.Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyl‐transferases . Carcinogenesis , 14 , 1633 – 1638 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 22).Shinohara , A. , Yamazoe , Y. , Saito , K. , Kamataki , T. and Kato , R.Species differences in the N‐acetylation by liver cytosol of mutagenic heterocyclic aromatic amines in protein pyrolysates . Carcinogenesis , 5 , 683 – 686 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 23).Mulder , G. J. and Scholtens , E.Phenol sulphotransferase and uridine diphosphate glucuronyltransferase from rat liver in vivo and in vitro: 2,6‐dichloro‐4‐nitrophenol as selective inhibitor of sulphation . Biochem. J. , 165 , 553 – 559 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24).Kato , R.Metabolic activation of mutagenic heterocyclic amines from protein pyrolysates . CRC Crit. Rev. Toxicol. , 16 , 307 – 348 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 25).Yamazoe , Y. , Abu‐Zeid , M. , Manabe , S. , Toyama , S. and Kato , R.Metabolic activation of a protein pyrolysate promutagen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) by rat liver microsomes and purified cytochrome P‐450 . Carcinogenesis , 9 , 105 – 109 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 26).Ozawa , S. , Abu‐Zeid , M. , Murayama , N. , Yamazoe , Y. and Kato , R.Decrease in the metabolic activating capacities of arylamines in livers bearing hyperplastic nodules: association with the selective changes in hepatic P‐450 isozymes . Jpn. J. Cancer Res. , 81 , 247 – 252 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27).Sjödin , P. , Wallen , H. , Alexander , J. and Jägerstad , M.Disposition and metabolism of the food mutagen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) in rats . Carcinogenesis , 10 , 1269 – 1275 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 28).Turesky , R. J. , Markovic , J. , Bracco‐Hammer , I. and Fay , L. B.The effect of dose and cytochrome P450 induction on the metabolism and disposition of the food‐borne carcinogen 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) in the rat . Carcinogenesis , 12 , 1847 – 1855 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 29).Luks , H. J. , Spratt , T. E. , Vavrek , M. T. , Roland , S. F. and Weisburger , J. H.Identification of sulfate and glucuronic acid conjugates of the 5‐hydroxy derivative as major metabolites of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in rats . Cancer Res. , 49 , 4407 – 4411 ( 1989. ). [PubMed] [Google Scholar]
  • 30).Adamson , R. H. , Thorgeirsson , U. P. , Snyderwine , E. G. , Thorgeirsson , S. S. , Reeves , J. , Dalgard , D. W. , Takayama , S. and Sugimura , T.Carcinogenicity of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in nonhuman primates: induction of tumors in three macaques . Jpn. J. Cancer Res. , 81 , 10 – 14 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31).Davis , C. D. , Schut , H. A. and Snyderwine , E. G.Enzymatic phase II activation of the N‐hydroxylamines of IQ, MeIQx and PhIP by various organs of monkey and rats . Carcinogenesis , 14 , 2091 – 2096 ( 1993. ). [DOI] [PubMed] [Google Scholar]

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