Rat nasal tissue activation of benzo(a)pyrene and 2-aminoanthracene to mutagens in Salmonella typhimurium.

Cytochrome P-450-dependent monooxygenase activity has been measured in the nasal turbinates of dogs and rats. The capacity of male Fischer-344 rat nasal tissue to bioactivate benzo(a)pyrene (BaP) and 2-aminoanthracene (2-AA) to mutagens in Salmonella typhimurium was investigated. 2-AA was mutagenic in strains TA98 and TA100 when nasal tissue S-9 was utilized as the activating enzyme system and BaP was mutagenic in strain TA100. At all doses and protein concentrations tested, 2-AA displayed nearly 500-1000 times greater bacterial mutagenicity than BaP. In strain TA-100, nasal tissue S-9 was approximately twice as active toward 2-AA as lung S-9 and 75% as active as liver S-9. Aryl hydrocarbon hydroxylase activity was detected in rat nasal tissue when 14C-BaP was used as a substrate. Rat nasal tissue metabolized BaP to several oxidized metabolites which included dihydrodiols, quinones, and phenols. 3-Hydroxybenzo(a)pyrene and BaP-3, 6-quinone were the major metabolites detected (150 pmoles/mg protein/30 min). These results indicate that rat nasal tissue can metabolize promutagens to reactive species which may play an important role in xenobiotic-induced nasal tumors.