Potent tumorigenicity of 7-chlorobenz[a]anthracene and 7-bromobenz[a]anthracene in the neonatal B6C3F(1) male mouse

The tumorigenicity of 7-chlorobenz[alpha]anthracene (7-Cl-BA), an environmental contaminant, and 7-bromobenz[alpha]anthracene (7-Br-BA) was determined in the male B6C3F(1) newborn mouse. Mice receiving 7-Cl-BA and 7-Br-BA by i.p. injec tions at a dose of 1600 nmol per mouse on 1, 8, and 15 days after birth developed 92 and 96% hepatocellular adenomas, and 100 and 83% hepatocellular carcinoma, respectively. Metabolism by liver microsomes of 15-day-old mice each produced the corresponding trans-3,4-dihydrodiol. Analysis by P-32-postlabeling/HPLC indicated the presence of DNA adducts derived from 7-Cl-BA trans-3,4-dihydrodiol and 7-Br-BA trans-3,4-dihydrodiol. Our results indicate that both 7-Cl-BA and 7-Br-BA are potent carcinogens and that bay-region diol epoxides are the ultimate metabolites that lead to DNA adduct formation and tumor initiation.