Abstract

We have recently shown that rat CYP2J4 is inducible by pyrazole in liver, small intestine, and olfactory mucosa. The aim of the present study was to determine whether mouse CYP2Js are also inducible by pyrazole, which was known to induce CYP2A5 in mouse liver and kidney, but not in lung or olfactory mucosa. CYP2J proteins were detected in mouse liver, lung, kidney, heart, eye, olfactory mucosa, and small intestine by immunoblot analysis with an anti-CYP2J4 antibody. The microsomal level of the CYP2J4-related P450s in various mouse tissues ranked in the order of small intestine > olfactory mucosa > liver > kidney ≥ heart > lung > eye. Induction of the CYP2J proteins was observed in the eye, liver, lung, kidney, olfactory mucosa, and small intestine, but not in the heart, after daily i.p. injection of pyrazole at 120 or 200 mg/kg for 3 days. CYP2J proteins were induced similarly in C57BL/6 and DBA/2 mice. CYP2A5 was detected in the small intestine in addition to liver and olfactory mucosa; however, treatment with pyrazole induced CYP2A5 in the liver, but not in the olfactory mucosa or the small intestine. Induction of CYP2J mRNAs was also observed by RNA blot analysis with a CYP2J4 cDNA probe. RNA-polymerase chain reaction analysis showed that, in both untreated and pyrazole-treated mice, CYP2J5 was expressed in the kidney and liver, but not in the other tissues examined, whereas CYP2J6 was detected in all tissues examined. The different tissue selectivities in CYP2A5 and CYP2J induction by pyrazole suggest involvement of different regulatory mechanisms.