Effect of vitamin E dietary intake on in vitro activation of aflatoxin B1.
The molecular mechanism of action of vitamin E on mammalian cells remains to be elucidated. In this study, vitamin E dietary intake was assessed for its effects on the initiation phase of carcinogenesis. We have conducted a dose-effect relationship between vitamin E dietary intake and aflatoxin B1 (AFB1) genotoxicity measured in vitro. Thus AFB1 induced 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-tocopherol for 8 weeks. Modulation of vitamin E level in postmitochondrial and microsomal fractions resulted in nutritional effects. Cytochrome P-450 content was not modified by the level of vitamin E in the diet. The microsomal P-450 activities, P-450 IIB1 and IIIA, were decreased in the deficient group to -35% and -16%, respectively, as compared with 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 formation 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 peroxidation 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.
Cassand
P
P
Laboratoire de Toxicologie Alimentaire, Université Bordeaux I, Talence, France.
Decoudu
S
S
Lévêque
F
F
Daubèze
M
M
Narbonne
J F
JF
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism
D014810:Vitamin E; D016604:Aflatoxin B1