Tumorigenicity of 7, 12-dimethylbenz[a]anthracene, its hydroxy-methylated derivatives and selected dihydrodiols in the newborn mouse

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Abstract
The newborn mouse lung adenoma model has been shown to be a sensitive test for studying the tumor-igenicity of bay region diol epoxides and their precursor dihydrodiols. When a total dose of 28 nmol of 7, 12-dimethylbenz[a]anthracene (DMBA) or its derivatives was injected i.p. into the preweaning mice, it was found that the 3, 4-dihydrodiols of both DMBA and 7-hy-droxymethyl-12-methylbenz[a]anthracene caused 13.3 and 4.1 times more lung adenomas than DMBA, respectively. The mice treated with the 5, 6- and 8, 9-dihydro-diols of DMBA, 7-hydroxymethyl-12-methylbenz[a]-anthracene and its 5, 6- 8,9- and 10,11-dihydrodiols, 7-methyl-12-hydroxymethylbenz[a]an-thracene and 7,12-dihydroxymethylbenz[a]anthracene developed a level of lung adenomas/mouse less than Mold higher than that found in the DMSO-treated control group. Liver tumors also developed in some of the mice. The percentage of mice with liver tumors also indicated that the 3, 4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracene were more tumorigenic than DMBA itself. These data indicate that the 3, 4-dihydrodiols of both DMBA and its 7-hydroxymethyl derivative may be proximate carcinogenic metabolites of DMBA in the newborn mouse.

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