P. Guerre et al., Effects of AFB1 on CYP 1A1, 1A2 and 3A6 mRNA, and P450 expression in primary culture of rabbit hepatocytes, TOX LETT, 111(3), 2000, pp. 243-251
Although numerous studies report strong hepatic cytochrome P450 decrease du
ring aflatoxicosis, the mechanisms involved in this decrease remain to be e
stablished. The purpose of this work is to investigate whether decreased CY
P mRNA expression could explain decreased P450 expression and activity. Stu
dies were conducted in primary cultures of rabbit hepatocytes exposed to 0.
1 and 1 mu M aflatoxin B1 (AFB1) incubated in the culture medium for 72 h.
In order to confirm the effects of the mycotoxin, 30 mu M beta-naphthoflavo
ne or rifampicin were used as respective inductors of P450 1A1 and 1A2 or 3
A6. Dose-dependent decreases of CYP mRNA expression were observed in all AF
B1-treated cells; however, these decreases were not specific. Moreover, P45
0 expression and activity are far less decreased by the AFB1 treatment than
their corresponding mRNA. Taken together, these results suggest that the s
pecific P450 decrease observed during aflatoxicosis was not the consequence
of a specific decrease of their mRNA expression. (C) 2000 Elsevier Science
Ireland Ltd. All rights reserved.