Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene

Shantu Amin, Dhimant Desai, Stephen S. Hecht

Research output: Contribution to journalArticle

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Abstract

Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-di-hydroxy-2,1-epoxy-4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.

Original languageEnglish (US)
Pages (from-to)2033-2037
Number of pages5
JournalCarcinogenesis
Volume14
Issue number10
DOIs
StatePublished - Oct 1 1993

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Epoxy Compounds
Skin
Neoplasms
Hydrocarbons
Carcinogens
Polycyclic Aromatic Hydrocarbons
Metabolic Networks and Pathways
benzo(c)phenanthrene
1,2-dihydroxy-5,6-dimethyl-3,4-epoxy-1,2,3,4-tetrahydrochrysene
5,6-dimethylchrysene
DNA

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

@article{a15b67b44298454ca6ca288a79b3bbe6,
title = "Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene",
abstract = "Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-di-hydroxy-2,1-epoxy-4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.",
author = "Shantu Amin and Dhimant Desai and Hecht, {Stephen S.}",
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Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene. / Amin, Shantu; Desai, Dhimant; Hecht, Stephen S.

In: Carcinogenesis, Vol. 14, No. 10, 01.10.1993, p. 2033-2037.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene

AU - Amin, Shantu

AU - Desai, Dhimant

AU - Hecht, Stephen S.

PY - 1993/10/1

Y1 - 1993/10/1

N2 - Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-di-hydroxy-2,1-epoxy-4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.

AB - Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-di-hydroxy-2,1-epoxy-4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.

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