Enhancing effect of a bay region methyl group on tumorigenicity in newborn mice and mouse skin of enantiomeric bay region diol epoxides formed stereoselectively from methylchrysenes in mouse epidermis

Stephen S. Hecht, Shantu Amin, Keith Huie, Assieh A. Melikian, Ronald G. Harvey

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Abstract

The stereochemistry of diol epoxide formation in mouse epidermis upon topical application of (3H]-l/R, 2/R-dihydroxy-l, 2-dihydro-5-methylchrysene ([3H]5-MeC-1/R,2R-diol) and [3H]-4-MeC-1R, 2R-diol, and the tumorigenicity in mouse skin and in newborn mice of the R, S, S, R and S, R, R, S enantiomers of 1, 2-dihydroxy-3, 4-epoxy-1, 2, 3, 4-tetrahydro-5-methykrhrysene (5-MeC-1, 2-diol-3, 4-epoxide), 5-MeC-7, 8-diol-9, 10-epoxide, and 6-MeC-1, 2-diol-3, 4-epoxide were examined. Analysis of tetraols and their derived tetraacetates present in mouse epidermis, 2 h after application of application of [3H]-5-MeC-1R,2R-diol-6-MeC-1R, 2R-diol, demonstrated greater than 90% stereoselectivity in formation of 5-MeC-1R,2S-diol-3S,4Repoxide and 6-MeC-1 R, 25-diol-35, 4Repoxide. Taken together with previous data, these results demonstrate that there is a high degree of stereoselectivity for formation of R, S, S, R enantiomers of 5-MeC- and 6-MeC-1, 2-diol-3, 4-epoxides in mouse skin. The results of the tumorigenicity studies in mouse skin and in newborn mice clearly demonstrated that 5-MeC-1 R, 2S-diol-3S, 4Repoxide was the most tumorigenic of the diol epoxide enantiomers tested; 6-MeC-1 R, 2S-diol-35, 4/Repoxide was inactive. The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC- 1/f, 25-diol-35, 4/Repoxide which, in contrast to 6-MeC-1/R, 25-diol-35, 4/Repoxide, has a methyl group in the same bay region as the epoxide ring. We propose that such methyl bay region diol epoxides of other carcinogenic methylated polynuclear aromatic hydrocarbons will also show unique tumorigenic properties.

Original languageEnglish (US)
Pages (from-to)5310-5315
Number of pages6
JournalCancer Research
Volume47
Issue number20
StatePublished - Jan 1 1987

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Epoxy Compounds
Epidermis
Skin
Polycyclic Aromatic Hydrocarbons

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{23e5c84bb41247d8ae1a67f40b23785e,
title = "Enhancing effect of a bay region methyl group on tumorigenicity in newborn mice and mouse skin of enantiomeric bay region diol epoxides formed stereoselectively from methylchrysenes in mouse epidermis",
abstract = "The stereochemistry of diol epoxide formation in mouse epidermis upon topical application of (3H]-l/R, 2/R-dihydroxy-l, 2-dihydro-5-methylchrysene ([3H]5-MeC-1/R,2R-diol) and [3H]-4-MeC-1R, 2R-diol, and the tumorigenicity in mouse skin and in newborn mice of the R, S, S, R and S, R, R, S enantiomers of 1, 2-dihydroxy-3, 4-epoxy-1, 2, 3, 4-tetrahydro-5-methykrhrysene (5-MeC-1, 2-diol-3, 4-epoxide), 5-MeC-7, 8-diol-9, 10-epoxide, and 6-MeC-1, 2-diol-3, 4-epoxide were examined. Analysis of tetraols and their derived tetraacetates present in mouse epidermis, 2 h after application of application of [3H]-5-MeC-1R,2R-diol-6-MeC-1R, 2R-diol, demonstrated greater than 90{\%} stereoselectivity in formation of 5-MeC-1R,2S-diol-3S,4Repoxide and 6-MeC-1 R, 25-diol-35, 4Repoxide. Taken together with previous data, these results demonstrate that there is a high degree of stereoselectivity for formation of R, S, S, R enantiomers of 5-MeC- and 6-MeC-1, 2-diol-3, 4-epoxides in mouse skin. The results of the tumorigenicity studies in mouse skin and in newborn mice clearly demonstrated that 5-MeC-1 R, 2S-diol-3S, 4Repoxide was the most tumorigenic of the diol epoxide enantiomers tested; 6-MeC-1 R, 2S-diol-35, 4/Repoxide was inactive. The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC- 1/f, 25-diol-35, 4/Repoxide which, in contrast to 6-MeC-1/R, 25-diol-35, 4/Repoxide, has a methyl group in the same bay region as the epoxide ring. We propose that such methyl bay region diol epoxides of other carcinogenic methylated polynuclear aromatic hydrocarbons will also show unique tumorigenic properties.",
author = "Hecht, {Stephen S.} and Shantu Amin and Keith Huie and Melikian, {Assieh A.} and Harvey, {Ronald G.}",
year = "1987",
month = "1",
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language = "English (US)",
volume = "47",
pages = "5310--5315",
journal = "Cancer Research",
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Enhancing effect of a bay region methyl group on tumorigenicity in newborn mice and mouse skin of enantiomeric bay region diol epoxides formed stereoselectively from methylchrysenes in mouse epidermis. / Hecht, Stephen S.; Amin, Shantu; Huie, Keith; Melikian, Assieh A.; Harvey, Ronald G.

In: Cancer Research, Vol. 47, No. 20, 01.01.1987, p. 5310-5315.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhancing effect of a bay region methyl group on tumorigenicity in newborn mice and mouse skin of enantiomeric bay region diol epoxides formed stereoselectively from methylchrysenes in mouse epidermis

AU - Hecht, Stephen S.

AU - Amin, Shantu

AU - Huie, Keith

AU - Melikian, Assieh A.

AU - Harvey, Ronald G.

PY - 1987/1/1

Y1 - 1987/1/1

N2 - The stereochemistry of diol epoxide formation in mouse epidermis upon topical application of (3H]-l/R, 2/R-dihydroxy-l, 2-dihydro-5-methylchrysene ([3H]5-MeC-1/R,2R-diol) and [3H]-4-MeC-1R, 2R-diol, and the tumorigenicity in mouse skin and in newborn mice of the R, S, S, R and S, R, R, S enantiomers of 1, 2-dihydroxy-3, 4-epoxy-1, 2, 3, 4-tetrahydro-5-methykrhrysene (5-MeC-1, 2-diol-3, 4-epoxide), 5-MeC-7, 8-diol-9, 10-epoxide, and 6-MeC-1, 2-diol-3, 4-epoxide were examined. Analysis of tetraols and their derived tetraacetates present in mouse epidermis, 2 h after application of application of [3H]-5-MeC-1R,2R-diol-6-MeC-1R, 2R-diol, demonstrated greater than 90% stereoselectivity in formation of 5-MeC-1R,2S-diol-3S,4Repoxide and 6-MeC-1 R, 25-diol-35, 4Repoxide. Taken together with previous data, these results demonstrate that there is a high degree of stereoselectivity for formation of R, S, S, R enantiomers of 5-MeC- and 6-MeC-1, 2-diol-3, 4-epoxides in mouse skin. The results of the tumorigenicity studies in mouse skin and in newborn mice clearly demonstrated that 5-MeC-1 R, 2S-diol-3S, 4Repoxide was the most tumorigenic of the diol epoxide enantiomers tested; 6-MeC-1 R, 2S-diol-35, 4/Repoxide was inactive. The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC- 1/f, 25-diol-35, 4/Repoxide which, in contrast to 6-MeC-1/R, 25-diol-35, 4/Repoxide, has a methyl group in the same bay region as the epoxide ring. We propose that such methyl bay region diol epoxides of other carcinogenic methylated polynuclear aromatic hydrocarbons will also show unique tumorigenic properties.

AB - The stereochemistry of diol epoxide formation in mouse epidermis upon topical application of (3H]-l/R, 2/R-dihydroxy-l, 2-dihydro-5-methylchrysene ([3H]5-MeC-1/R,2R-diol) and [3H]-4-MeC-1R, 2R-diol, and the tumorigenicity in mouse skin and in newborn mice of the R, S, S, R and S, R, R, S enantiomers of 1, 2-dihydroxy-3, 4-epoxy-1, 2, 3, 4-tetrahydro-5-methykrhrysene (5-MeC-1, 2-diol-3, 4-epoxide), 5-MeC-7, 8-diol-9, 10-epoxide, and 6-MeC-1, 2-diol-3, 4-epoxide were examined. Analysis of tetraols and their derived tetraacetates present in mouse epidermis, 2 h after application of application of [3H]-5-MeC-1R,2R-diol-6-MeC-1R, 2R-diol, demonstrated greater than 90% stereoselectivity in formation of 5-MeC-1R,2S-diol-3S,4Repoxide and 6-MeC-1 R, 25-diol-35, 4Repoxide. Taken together with previous data, these results demonstrate that there is a high degree of stereoselectivity for formation of R, S, S, R enantiomers of 5-MeC- and 6-MeC-1, 2-diol-3, 4-epoxides in mouse skin. The results of the tumorigenicity studies in mouse skin and in newborn mice clearly demonstrated that 5-MeC-1 R, 2S-diol-3S, 4Repoxide was the most tumorigenic of the diol epoxide enantiomers tested; 6-MeC-1 R, 2S-diol-35, 4/Repoxide was inactive. The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC- 1/f, 25-diol-35, 4/Repoxide which, in contrast to 6-MeC-1/R, 25-diol-35, 4/Repoxide, has a methyl group in the same bay region as the epoxide ring. We propose that such methyl bay region diol epoxides of other carcinogenic methylated polynuclear aromatic hydrocarbons will also show unique tumorigenic properties.

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