Inhibitory effect of alpha-tocopherol on benzo(a)pyrene-induced CYPA1 activity in rat liver.
Combined treatment with benzo(a)pyrene (classic inductor of cytochromes P450 of subfamily 1A, CYPA1 and CYP1A2) and alpha-tocopherol decreased benzo(a)pyrene-induced CYP1A1 activity in rat liver. Activities of CYP1A2, NADPH-cytochrome P450 reductase, and glutathione S-transferase remained unchanged under these conditions. Addition of alpha-tocopherol to benzo(a)pyrene-induced microsomes in vitro decreased activity of CYP1A1. Immunoblotting of proteins in liver microsomes with antibodies against CYP1A1 did not reveal differences in CYP1A1 protein content in the liver of rats receiving benzo(a)pyrene alone or in combination with alpha-tocopherol. The in vivo decrease in benzo(a)pyrene-induced CYP1A1 activity did not result from free radical-produced damage to CYP1A1. The inhibition of benzo(a)pyrene-induced CYP1A1 activity with alpha-tocopherol is probably realized at the posttranslational level.
Sidorova
Yu A
YA
Laboratory for Biochemistry of Foreign Compounds, Institute of Molecular Biology and Biophysics, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk. ysidorova@soraramn.ru
Grishanova
A Yu
AY
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D003580:Cytochromes; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000378:metabolism*
D003580:Cytochromes; D015262:Xenobiotics; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase; D024502:alpha-Tocopherol