Mutagenesis induced by benzo[a]pyrene in lacZ mouse mammary and oral tissues: comparisons with mutagenesis in other organs and relationships to previous carcinogenicity assays

Thus far, in vivo mutagenic assays have detected organ-specific effects of benzo[a]pyrene (B[a]P) in a number of organs, but not in oral tissues and breast. Previous studies have shown that the mouse tongue is a target for tumorigenesis induced by B[a]P when incorporated into feed, and polycyclic aromatic hydrocarbons are carcinogens in mouse mammary tissue. In order to evaluate the capacity of the lacZ mouse in vivo mutagenesis assay to detect mutations in these target tissues, we have measured mutagenesis induced by B[a]P in breast and oral tissues. The oral tissue consisted of either tongue or a mixture of oral tissues from several sites in the oral cavity. B[a]P was more mutagenic in breast tissue than in most other organs tested (liver, lung and kidney) when administered at relatively high dose by gavage, and more mutagenic than in liver, but not lung, at low dose. When administered in an emulsion in drinking water, B[a]P was more mutagenic in oral tissues than in liver, and somewhat less mutagenic than in lung. Regardless of dose, the mutagenic activity was greatest in colon where it was much higher than in other organs. A reasonable correlation was observed between mutagenesis observed here and carcinogenesis in previous studies although some differences were noted. To our knowledge, this represents the first report of in vivo mutagenesis in non-tumor mammary and oral tissue, and the results indicate these organs can efficiently metabolize B[a]P to genotoxic products, although some transport of active metabolites from the liver cannot be ruled out. The lacZ mouse mutagenesis assay may represent a shorter term alternative to carcinogenesis assays for investigations of factors affecting initiation of carcinogenesis in mammary and oral tissues. However, it is less predictive of actual tumor formation.