EFFECT OF CIGARETTE-SMOKE ON CYP1A1, CYP1A2 AND CYP2B1 2 OF NASAL MUCOSAE IN F344 RATS/

Enzymes of the nasal tissue, one of the first tissues to contact inhal ed toxicants, are relatively resistant to induction by traditional ind ucers. Because tobacco smoke has been shown to induce cytochrome P450 1A1 (CYP1A1) in rat and human lung tissue, we hypothesized that it wou ld also alter levels of xenobiotic-metabolizing enzymes in nasal mucos ae, In the present study, the effect of mainstream cigarette smoke (MC S) on nasal CYP1A1, CYP1A2 and CYP2B1/2 was explored. Four groups of 3 0 F344 rats were exposed to MCS (100 mg total particulate matter/m(3)) or filtered air for 2 or 8 weeks. Western analysis of microsomes from nasal tissue of MCS-exposed rats showed an induction of CYP1A1 in res piratory and olfactory mucosae, as well as liver, kidney and lung. Rel ative to controls, CYP1A2 levels increased slightly in the liver and o lfactory mucosa. CYP2B1/2, which increased in the liver, appeared to d ecrease in upper and lower respiratory tissues. Little to no immunorea ctivity with CYP1A1 antibody was observed in fixed nasal sections of c ontrol rats, yet intense immunoreactivity was seen in epithelia throug hout the nasal cavity of MCS-exposed rats. Ethoxyresorufin O-deethylas e activity (associated with CYP1A1/2) decreased similar to 2-fold in o lfactory mucosa, but increased in non-nasal tissues of rats exposed to MCS, Methoxy-and pentoxyresorufin O-dealkylase activities (associated with CYP1A2 and CYP2B1/2, respectively) decreased in olfactory and re spiratory mucosae, as well as lung (CYP2B1/2), yet increased in liver. These data suggest that xenobiotic-metabolizing enzymines of the nasa l mucosae may be regulated differently than other tissues.