Effects of AFB1 on CYP 1A1, 1A2 and 3A6 mRNA, and P450 expression in primary culture of rabbit hepatocytes

• Published in: Toxicology letters Vol. 111; no. 3; pp. 243 - 251
• Main Authors: Guerre, P, Pineau, T, Costet, P, Burgat, V, Galtier, P
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.01.2000; Amsterdam Elsevier Science
• Subjects: Aflatoxin B1; Aflatoxin B1 - pharmacology; Animals; Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cells, Cultured; CYP mRNA; CYP1A1 protein; CYP1A2 protein; Cytochrome P-450 CYP1A1 - biosynthesis; Cytochrome P-450 CYP1A2 - biosynthesis; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P450; Drug metabolizing enzyme; Food industries; Food toxicology; Fundamental and applied biological sciences. Psychology; Hepatocytes; L-Lactate Dehydrogenase - metabolism; Liver; Liver - cytology; Liver - drug effects; Liver - enzymology; Medical sciences; Monooxygenase; mRNA; Rabbit; Rabbits; RNA, Messenger - biosynthesis; Toxicology; Drug metabolizing enzyme; Hepatocytes; Cytochrome P450; Liver; Aflatoxin B1; Rabbit; CYP mRNA; Monooxygenase; Enzyme; Isozyme; Toxicity; Mycotoxin; Cytotoxicity; Lagomorpha; In vitro; Toxin; Vertebrata; Mammalia; Enzymatic activity; Hepatocyte; Animal; Primary culture; Digestive diseases; Drug-metabolizing enzyme
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(99)00181-2

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 μM aflatoxin B1 (AFB1) incubated in the culture medium for 72 h. In order to confirm the effects of the mycotoxin, 30 μM β-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.