Tumorigenicity of 5-Methylchrysene Dihydrodiols and Dihydrodiol Epoxides in Newborn Mice and on Mouse Skin

Stephen S. Hecht, Lynn Radok, Shantu Amin, Keith Huie, Assieh A. Melikian, Dietrich Hoffmann, John Pataki, Ronald G. Harvey

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67 Scopus citations

Abstract

5-Methylchrysene, (±-trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene, (±-trans-7,8-dihydro-7,8-dihydroxy-5-methyl-chrysene, (±)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetra-hydro-5-methylchrysene (anti-DE-l), (±trans-1,2-dihydroxy-«yr?-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (syn-DE-l), and (±trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (anti-DE-ll) were tested for tumorigenicity in newborn mice and for tumor-initiating activity on mouse skin. In newborn mice, a total dose of 56 nmol of anti-DE-l induced 4.6 lung tumors/mouse and 1.2 liver tumors/mouse. These incidences were significantly higher than observed for any of the other metabolites, tested at equimolar doses. The results indicate that anti-DE-l, but not syn-DE-l or anti-DE-ll, is a major ultimate carcinogen of 5-methylchrysene in the newborn mouse. Anti-DE-l was also more tumorigenic than anti-DE-lf on mouse skin, inducing 4.4 tumors/mouse after an initiating dose of 100 nmol, compared to zero tumors per mouse induced by anti-DE-II. However, anti-DE-l was less tumorigenic on mouse skin than was its metabolic precursor, trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene or its parent hydrocarbon, 5-methylchrysene.

Original languageEnglish (US)
Pages (from-to)1449-1452
Number of pages4
JournalCancer Research
Volume45
Issue number4
StatePublished - Apr 1 1985

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    Hecht, S. S., Radok, L., Amin, S., Huie, K., Melikian, A. A., Hoffmann, D., Pataki, J., & Harvey, R. G. (1985). Tumorigenicity of 5-Methylchrysene Dihydrodiols and Dihydrodiol Epoxides in Newborn Mice and on Mouse Skin. Cancer Research, 45(4), 1449-1452.