Rat nasal tissue activation of benzo(a)pyrene and 2‐aminoanthracene to mutagens in salmonella typhimurium

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Abstract
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 TA 100 when nasal tissue S‐9 was utilized as the activating enzyme system and BaP was mutagenic in strain TA 100. 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.