Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1

Tsutomu Shimada, Carrie L. Hayes, Hiroshi Yamazaki, Shantu Amin, Stephen S. Hecht, F. Peter Guengerich, Thomas R. Sutter

Research output: Contribution to journalArticle

720 Citations (Scopus)

Abstract

A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae, and the microsomes containing P450 1B1 were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 1B1 with those catalyzed by recombinant human P450s 1A1 and 1A2, which were purified from membranes of Escherichia coli. The carcinogenic chemicals tested included 27 polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, N-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 1B1 was found to have the highest catalytic activities for the activation of 11,12-dihydroxy-11,12- dihydrodibenzo[a,l]pyrene, 1,2-dihydroxy-1,2-dihydro-5-methylchrysene, (+)- 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, 11,12-dihydroxy-11,12- dihydrobenzo[g]chrysene, 3,4-dihydroxy-3,4-dihydrobenzo[c]phenanthrene, 3- amino-1,4-dimethyl-5H-pyrido[4,3-b]iodole, 2-aminoanthracene, 3-methoxy-4- aminoazobenzene, and 2-nitropyrene. P450 1B1 also catalyzed the activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-aminofluorene, 6-aminochrysene and its 1,2-dihydrodiol, (-)-7,8-dihydroxy- 7,8-dihydrobenzo[a]pyrene, 1,2-dihydroxy-1,2-dihydrochrysene, 1,2-dihydroxy- 1,2-dihydro-5,6-dimethylchrysene, 2,3-dihydroxy-2,3-dihydrofluoranthene, 3,4- dihydroxy-3,4-dihydro-7,12-dimethylbenz[a]anthracene, and 6-nitrochrysene to appreciable extents. However, P450 1B1 did not produce genotoxic products from benzo[a]pyrene, trans-3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenzo[a]anthracene, 7,12- dimethylbenz[a]anthracene and its cis-5,6-dihydrodiol, 5-methylchrysene, 11,12-dihydroxy-11,12-dihydro-3-methylcholanthrene, 1,2-dihydroxy-1,2- dihydro-6-methylchrysene, benzo[c]phenanthrene, 2-amino-6- methyldipyrido[1,2-a:3',2'-d]imidazole, 2-acetylaminofluorene, benzidine, 2- naphthylamine, aflatoxin B1, aflatoxin G1, sterigmatocystin, N- nitrosodimethylamine, vinyl carbamate, or acrylonitrile in this assay system. P450 1B1 is expressed constitutively in extrahepatic organs, including fetal tissue samples, and is highly inducible in various organs by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds in experimental animal models. Thus, activation of procarcinogens by P450 1B1 may contribute to human tumors of extrahepatic origin.

Original languageEnglish (US)
Pages (from-to)2979-2984
Number of pages6
JournalCancer Research
Volume56
Issue number13
StatePublished - Jul 1 1996

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Cytochrome P-450 Enzyme System
Acrylonitrile
Dimethylnitrosamine
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
2-amino-3-methylimidazo(4,5-f)quinoline
2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole
Sterigmatocystin
2-Naphthylamine
Environmental Carcinogens
2-Acetylaminofluorene
Aflatoxin B1
Enzyme Activation
Methylcholanthrene
Mycotoxins
Benzo(a)pyrene
Polycyclic Aromatic Hydrocarbons
Mutagens
Salmonella typhimurium
Hydrocarbons
Microsomes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shimada, T., Hayes, C. L., Yamazaki, H., Amin, S., Hecht, S. S., Guengerich, F. P., & Sutter, T. R. (1996). Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Research, 56(13), 2979-2984.
Shimada, Tsutomu ; Hayes, Carrie L. ; Yamazaki, Hiroshi ; Amin, Shantu ; Hecht, Stephen S. ; Guengerich, F. Peter ; Sutter, Thomas R. / Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. In: Cancer Research. 1996 ; Vol. 56, No. 13. pp. 2979-2984.
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abstract = "A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae, and the microsomes containing P450 1B1 were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 1B1 with those catalyzed by recombinant human P450s 1A1 and 1A2, which were purified from membranes of Escherichia coli. The carcinogenic chemicals tested included 27 polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, N-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 1B1 was found to have the highest catalytic activities for the activation of 11,12-dihydroxy-11,12- dihydrodibenzo[a,l]pyrene, 1,2-dihydroxy-1,2-dihydro-5-methylchrysene, (+)- 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, 11,12-dihydroxy-11,12- dihydrobenzo[g]chrysene, 3,4-dihydroxy-3,4-dihydrobenzo[c]phenanthrene, 3- amino-1,4-dimethyl-5H-pyrido[4,3-b]iodole, 2-aminoanthracene, 3-methoxy-4- aminoazobenzene, and 2-nitropyrene. P450 1B1 also catalyzed the activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-aminofluorene, 6-aminochrysene and its 1,2-dihydrodiol, (-)-7,8-dihydroxy- 7,8-dihydrobenzo[a]pyrene, 1,2-dihydroxy-1,2-dihydrochrysene, 1,2-dihydroxy- 1,2-dihydro-5,6-dimethylchrysene, 2,3-dihydroxy-2,3-dihydrofluoranthene, 3,4- dihydroxy-3,4-dihydro-7,12-dimethylbenz[a]anthracene, and 6-nitrochrysene to appreciable extents. However, P450 1B1 did not produce genotoxic products from benzo[a]pyrene, trans-3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenzo[a]anthracene, 7,12- dimethylbenz[a]anthracene and its cis-5,6-dihydrodiol, 5-methylchrysene, 11,12-dihydroxy-11,12-dihydro-3-methylcholanthrene, 1,2-dihydroxy-1,2- dihydro-6-methylchrysene, benzo[c]phenanthrene, 2-amino-6- methyldipyrido[1,2-a:3',2'-d]imidazole, 2-acetylaminofluorene, benzidine, 2- naphthylamine, aflatoxin B1, aflatoxin G1, sterigmatocystin, N- nitrosodimethylamine, vinyl carbamate, or acrylonitrile in this assay system. P450 1B1 is expressed constitutively in extrahepatic organs, including fetal tissue samples, and is highly inducible in various organs by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds in experimental animal models. Thus, activation of procarcinogens by P450 1B1 may contribute to human tumors of extrahepatic origin.",
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Shimada, T, Hayes, CL, Yamazaki, H, Amin, S, Hecht, SS, Guengerich, FP & Sutter, TR 1996, 'Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1', Cancer Research, vol. 56, no. 13, pp. 2979-2984.

Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. / Shimada, Tsutomu; Hayes, Carrie L.; Yamazaki, Hiroshi; Amin, Shantu; Hecht, Stephen S.; Guengerich, F. Peter; Sutter, Thomas R.

In: Cancer Research, Vol. 56, No. 13, 01.07.1996, p. 2979-2984.

Research output: Contribution to journalArticle

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T1 - Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1

AU - Shimada, Tsutomu

AU - Hayes, Carrie L.

AU - Yamazaki, Hiroshi

AU - Amin, Shantu

AU - Hecht, Stephen S.

AU - Guengerich, F. Peter

AU - Sutter, Thomas R.

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Y1 - 1996/7/1

N2 - A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae, and the microsomes containing P450 1B1 were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 1B1 with those catalyzed by recombinant human P450s 1A1 and 1A2, which were purified from membranes of Escherichia coli. The carcinogenic chemicals tested included 27 polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, N-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 1B1 was found to have the highest catalytic activities for the activation of 11,12-dihydroxy-11,12- dihydrodibenzo[a,l]pyrene, 1,2-dihydroxy-1,2-dihydro-5-methylchrysene, (+)- 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, 11,12-dihydroxy-11,12- dihydrobenzo[g]chrysene, 3,4-dihydroxy-3,4-dihydrobenzo[c]phenanthrene, 3- amino-1,4-dimethyl-5H-pyrido[4,3-b]iodole, 2-aminoanthracene, 3-methoxy-4- aminoazobenzene, and 2-nitropyrene. P450 1B1 also catalyzed the activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-aminofluorene, 6-aminochrysene and its 1,2-dihydrodiol, (-)-7,8-dihydroxy- 7,8-dihydrobenzo[a]pyrene, 1,2-dihydroxy-1,2-dihydrochrysene, 1,2-dihydroxy- 1,2-dihydro-5,6-dimethylchrysene, 2,3-dihydroxy-2,3-dihydrofluoranthene, 3,4- dihydroxy-3,4-dihydro-7,12-dimethylbenz[a]anthracene, and 6-nitrochrysene to appreciable extents. However, P450 1B1 did not produce genotoxic products from benzo[a]pyrene, trans-3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenzo[a]anthracene, 7,12- dimethylbenz[a]anthracene and its cis-5,6-dihydrodiol, 5-methylchrysene, 11,12-dihydroxy-11,12-dihydro-3-methylcholanthrene, 1,2-dihydroxy-1,2- dihydro-6-methylchrysene, benzo[c]phenanthrene, 2-amino-6- methyldipyrido[1,2-a:3',2'-d]imidazole, 2-acetylaminofluorene, benzidine, 2- naphthylamine, aflatoxin B1, aflatoxin G1, sterigmatocystin, N- nitrosodimethylamine, vinyl carbamate, or acrylonitrile in this assay system. P450 1B1 is expressed constitutively in extrahepatic organs, including fetal tissue samples, and is highly inducible in various organs by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds in experimental animal models. Thus, activation of procarcinogens by P450 1B1 may contribute to human tumors of extrahepatic origin.

AB - A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae, and the microsomes containing P450 1B1 were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 1B1 with those catalyzed by recombinant human P450s 1A1 and 1A2, which were purified from membranes of Escherichia coli. The carcinogenic chemicals tested included 27 polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, N-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 1B1 was found to have the highest catalytic activities for the activation of 11,12-dihydroxy-11,12- dihydrodibenzo[a,l]pyrene, 1,2-dihydroxy-1,2-dihydro-5-methylchrysene, (+)- 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, 11,12-dihydroxy-11,12- dihydrobenzo[g]chrysene, 3,4-dihydroxy-3,4-dihydrobenzo[c]phenanthrene, 3- amino-1,4-dimethyl-5H-pyrido[4,3-b]iodole, 2-aminoanthracene, 3-methoxy-4- aminoazobenzene, and 2-nitropyrene. P450 1B1 also catalyzed the activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-aminofluorene, 6-aminochrysene and its 1,2-dihydrodiol, (-)-7,8-dihydroxy- 7,8-dihydrobenzo[a]pyrene, 1,2-dihydroxy-1,2-dihydrochrysene, 1,2-dihydroxy- 1,2-dihydro-5,6-dimethylchrysene, 2,3-dihydroxy-2,3-dihydrofluoranthene, 3,4- dihydroxy-3,4-dihydro-7,12-dimethylbenz[a]anthracene, and 6-nitrochrysene to appreciable extents. However, P450 1B1 did not produce genotoxic products from benzo[a]pyrene, trans-3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenzo[a]anthracene, 7,12- dimethylbenz[a]anthracene and its cis-5,6-dihydrodiol, 5-methylchrysene, 11,12-dihydroxy-11,12-dihydro-3-methylcholanthrene, 1,2-dihydroxy-1,2- dihydro-6-methylchrysene, benzo[c]phenanthrene, 2-amino-6- methyldipyrido[1,2-a:3',2'-d]imidazole, 2-acetylaminofluorene, benzidine, 2- naphthylamine, aflatoxin B1, aflatoxin G1, sterigmatocystin, N- nitrosodimethylamine, vinyl carbamate, or acrylonitrile in this assay system. P450 1B1 is expressed constitutively in extrahepatic organs, including fetal tissue samples, and is highly inducible in various organs by 2,3,7,8- tetrachlorodibenzo-p-dioxin and related compounds in experimental animal models. Thus, activation of procarcinogens by P450 1B1 may contribute to human tumors of extrahepatic origin.

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Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, Guengerich FP et al. Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Research. 1996 Jul 1;56(13):2979-2984.