Title: Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs.
Authors: Black, V H; Wang, A F; Henry, M; Shaw, P M
Published In Arch Biochem Biophys, (1998 Jun 15)
Abstract: To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of 3,3'-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1 (53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3'-methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein comigrating with liver CYP1A1 was detected only after 3,3'-methylcholanthrene treatment. Protein comigrating with CYP1A2 was never detected in adrenal microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver, but not adrenal, after 3, 3'-methylcholanthrene treatment. Another immunoreactive protein (52 kDa), present constitutively in liver and adrenal microsomes, was not induced in either tissue by 3,3'-methylcholanthrene. The precise identities of the inducible 57-kDa and the noninducible 52-kDa proteins remain to be determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1 was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses demonstrated that, despite the fact that the 56-kDa protein was not detectable in adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals. Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following 3,3'-methylcholanthrene treatment, underscoring differences in the regulation of CYP1A expression in the two tissues. Levels of ethoxyresorufin and methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein, respectively.
PubMed ID: 9637727
MeSH Terms: Adrenal Glands/drug effects; Adrenal Glands/metabolism*; Animals; Blotting, Northern; Blotting, Western; Cytochrome P-450 CYP1A1/biosynthesis*; Cytochrome P-450 CYP1A2/biosynthesis*; Enzyme Induction/drug effects; Guinea Pigs; Humans; Liver/drug effects; Liver/metabolism; Male; Methylcholanthrene/pharmacology*; Polymerase Chain Reaction; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.