The molecular mechanism of action of vitamin E on mammalian cells rema
ins to be elucidated. In this study, vitamin E dietary intake was asse
ssed for its effects on the initiation phase of carcinogenesis. We hav
e conducted a dose-effect relationship between vitamin E dietary intak
e and aflatoxin B1 (AFB1) genotoxicity measured in vitro. Thus AFB1 in
duced mutagenesis in Salmonella typhimurium TA98 was investigated and
compared to effect of vitamin E dietary intake on hepatic microsomal P
-450 content and specific activities involved in AFB1 metabolism. Rats
were fed ad libitum a diet containing 0, 0.05, 0.5 or 5 IU of alpha-t
ocopherol for 8 weeks. Modulation of vitamin E level in postmitochondr
ial and microsomal fractions resulted in nutritional effects. Cytochro
me P-450 content was not modified by the level of vitamin E in the die
t. The microsomal P-450 activities, P-450 IIB1 and IIIA, were decrease
d in the deficient group to -35% and -16%, respectively, as compared w
ith control diet (0.05 IU). Diet supplemented with 0.5 IU of vitamin E
increased P-450 IIB and IIIA activities (+28% and +37%, respectively)
whereas a diet highly supplemented in vitamin E (5 IU) reduced these
specific P-450 activities. Lipid peroxidation, estimated by the format
ion of thiobarbituric acid reactive products, increased in the dietary
vitamin E free diet (+20%) and strongly decreased in the supplemented
group (-99%). This study establishes that in vivo, dietary vitamin E
protects directly membrane against damage induced by lipid peroxidatio
n and indirectly hepatic microsomal monooxygenase activities. However,
vitamin E accumulation seems to alter membrane structure and function
. The nutritional effect of vitamin E on hepatic microsomal cytochrome
P-450 activities modified the AFB1 genotoxicity measured in vitro.