High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols

Shantu Amin, Keith Huie, George Balanikas, Stephen S. Hecht, John Pataki, Ronald G. Harvey

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The stereoselectivity of mouse skin metabolic activation to dihydrodiols of the strong carcinogen 5-methylchrysene (5-MeC) and the weak carcinogen 6-methylchrysene (6-MeC) was investigated. Synthetic 1, 2-dihydro-l, 2-dihydroxy-5-methylchrysene (5-MeC-1, 2-diol), 5-MeC-7, 8-diol, and 6-MeC-1, 2-diol were resolved into their R, R-and S, S-enantiomers by chiral stationary phase high performance liquid chromatography. The absolute configurations of the enantiomers were assigned by their circular dichroism spectra. Using these enantiomers as standards, the metabolism of 5-MeC and 6-MeC in vitro in rat and mouse liver and in vivo in mouse epidermis was investigated. Only the R, R-enantiomers of each dihydrodiol predominated (>90%). The dihydrodiol enantiomers were tested for tumor initiating activity on mouse skin. In each case, the R,R-dihydrodiol enantiomer was significantly more tumorigenic than the S,S-enantiomer. The most tumorigenic compound was 5-MeC-1 Radiol; it was significantly more active than either 5-MeC-7 R,8R-diol or 6-MeC-1R,2R-diol. The results of this study demonstrate that there is a high degree of stereoselectivity in the metabolic activation of 5-MeC and 6-MeC to proximate tumorigenic dihydrodiols in mouse skin. The bay region methyl group has no effect on the stereoselectivity of activation to 1,2-dihydrodiol metabolites in the chrysene system.

Original languageEnglish (US)
Pages (from-to)3613-3617
Number of pages5
JournalCancer Research
Volume47
Issue number14
StatePublished - Jul 1987

Fingerprint

Skin
Carcinogens
5-methylchrysene
Metabolic Activation
trans-1,2-dihydro-1,2-naphthalenediol
Circular Dichroism
Epidermis
High Pressure Liquid Chromatography
6-methylchrysene
Liver
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Amin, S., Huie, K., Balanikas, G., Hecht, S. S., Pataki, J., & Harvey, R. G. (1987). High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols. Cancer Research, 47(14), 3613-3617.
Amin, Shantu ; Huie, Keith ; Balanikas, George ; Hecht, Stephen S. ; Pataki, John ; Harvey, Ronald G. / High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols. In: Cancer Research. 1987 ; Vol. 47, No. 14. pp. 3613-3617.
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abstract = "The stereoselectivity of mouse skin metabolic activation to dihydrodiols of the strong carcinogen 5-methylchrysene (5-MeC) and the weak carcinogen 6-methylchrysene (6-MeC) was investigated. Synthetic 1, 2-dihydro-l, 2-dihydroxy-5-methylchrysene (5-MeC-1, 2-diol), 5-MeC-7, 8-diol, and 6-MeC-1, 2-diol were resolved into their R, R-and S, S-enantiomers by chiral stationary phase high performance liquid chromatography. The absolute configurations of the enantiomers were assigned by their circular dichroism spectra. Using these enantiomers as standards, the metabolism of 5-MeC and 6-MeC in vitro in rat and mouse liver and in vivo in mouse epidermis was investigated. Only the R, R-enantiomers of each dihydrodiol predominated (>90{\%}). The dihydrodiol enantiomers were tested for tumor initiating activity on mouse skin. In each case, the R,R-dihydrodiol enantiomer was significantly more tumorigenic than the S,S-enantiomer. The most tumorigenic compound was 5-MeC-1 Radiol; it was significantly more active than either 5-MeC-7 R,8R-diol or 6-MeC-1R,2R-diol. The results of this study demonstrate that there is a high degree of stereoselectivity in the metabolic activation of 5-MeC and 6-MeC to proximate tumorigenic dihydrodiols in mouse skin. The bay region methyl group has no effect on the stereoselectivity of activation to 1,2-dihydrodiol metabolites in the chrysene system.",
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Amin, S, Huie, K, Balanikas, G, Hecht, SS, Pataki, J & Harvey, RG 1987, 'High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols', Cancer Research, vol. 47, no. 14, pp. 3613-3617.

High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols. / Amin, Shantu; Huie, Keith; Balanikas, George; Hecht, Stephen S.; Pataki, John; Harvey, Ronald G.

In: Cancer Research, Vol. 47, No. 14, 07.1987, p. 3613-3617.

Research output: Contribution to journalArticle

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Amin S, Huie K, Balanikas G, Hecht SS, Pataki J, Harvey RG. High Stereoselectivity in Mouse Skin Metabolic Activation of Methylchrysenes to Tumorigenic Dihydrodiols. Cancer Research. 1987 Jul;47(14):3613-3617.