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

The newborn mouse lung adenoma model has been shown to be asensitive test for studying the tumor-igenicity of bay regiondiol epoxides and their precursor dihydrodiols. When a totaldose of 28 nmol of 7, 12-dimethylbenz[a]anthracene (DMBA) orits 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]anthracenecaused 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-thraceneand 7,12-dihydroxymethylbenz[a]anthracene developed a levelof lung adenomas/mouse less than Mold higher than that foundin the DMSO-treated control group. Liver tumors also developedin some of the mice. The percentage of mice with liver tumorsalso indicated that the 3, 4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracenewere more tumorigenic than DMBA itself. These data indicatethat the 3, 4-dihydrodiols of both DMBA and its 7-hydroxymethylderivative may be proximate carcinogenic metabolites of DMBAin the newborn mouse.