Effects of AFB1 on CYP 1A1, 1A2 and 3A6 mRNA, and P450 expression in primary culture of rabbit hepatocytes.
Although numerous studies report strong hepatic cytochrome P450 decrease during aflatoxicosis, the mechanisms involved in this decrease remain to be established. The purpose of this work is to investigate whether decreased CYP mRNA expression could explain decreased P450 expression and activity. Studies were conducted in primary cultures of rabbit hepatocytes exposed to 0.1 and 1 microM aflatoxin B1 (AFB1) incubated in the culture medium for 72 h. In order to confirm the effects of the mycotoxin, 30 microM beta-naphthoflavone or rifampicin were used as respective inductors of P450 1A1 and 1A2 or 3A6. Dose-dependent decreases of CYP mRNA expression were observed in all AFB1-treated cells; however, these decreases were not specific. Moreover, P450 expression and activity are far less decreased by the AFB1 treatment than their corresponding mRNA. Taken together, these results suggest that the specific P450 decrease observed during aflatoxicosis was not the consequence of a specific decrease of their mRNA expression.
Guerre
P
P
Département des Sciences Biologiques et Fonctionnelles, Pharmacie-Toxicologie, ENVT, Toulouse, France.
Pineau
T
T
Costet
P
P
Burgat
V
V
Galtier
P
P
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D007770:L-Lactate Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C100638:cytochrome P-450 CYP3A6 (rabbit)