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 inhaled toxicants, are relatively resistant to induction by traditional inducers. Because tobacco smoke has been shown to induce cytochrome P450 1A1 (CYP1A1) in rat and human lung tissue, we hypothesized that it would also alter levels of xenobiotic-metabolizing enzymes in nasal mucosae. In the present study, the effect of mainstream cigarette smoke (MCS) on nasal CYP1A1, CYP1A2 and CYP2B1/2 was explored. Four groups of 30 F344 rats were exposed to MCS (100 mg total particulate matter/m3) 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 respiratory and olfactory mucosae, as well as liver, kidney and lung. Relative to controls, CYP1A2 levels increased slightly in the liver and olfactory mucosa. CYP2B1/2, which increased in the liver, appeared to decrease in upper and lower respiratory tissues. Little to no immunoreactivity with CYP1A1 antibody was observed in fixed nasal sections of control rats, yet intense immunoreactivity was seen in epithelia throughout the nasal cavity of MCS-exposed rats. Ethoxyresorufin O-deethylase activity (associated with CYP1A1/2) decreased approximately 2-fold in olfactory 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 respiratory mucosae, as well as lung (CYP2B1/2), yet increased in liver. These data suggest that xenobiotic-metabolizing enzymines of the nasal mucosae may be regulated differently than other tissues.
Wardlaw
S A
SA
Inhalation Toxicology Laboratory, Lovelace Respiratory Research Institute, Albuquerque, NM 87185, USA.
Nikula
K J
KJ
Kracko
D A
DA
Finch
G L
GL
Thornton-Manning
J R
JR
Dahl
A R
AR
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D007527:Isoenzymes; D012906:Smoke; D003577:Cytochrome P-450 Enzyme System