Tumorigenicity of 5-methylchrysene dihydrodiols and dihydrodiol epoxides in newborn mice and on mouse skin.

5-Methylchrysene, (+/-)-trans-1,2-dihydro-1,2-dihydroxy-5-methylchrysene, (+/-)-trans-7,8-dihydro-7,8-dihydroxy-5-methylchrysene, (+/-)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-DE-I), (+/-)-trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (syn-DE-I), and (+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (anti-DE-II) 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-I 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-I, but not syn-DE-I or anti-DE-II, is a major ultimate carcinogen of 5-methylchrysene in the newborn mouse. Anti-DE-I was also more tumorigenic than anti-DE-II 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-I 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.