Effect of vitamin A dietary intake on in vitro and in vivo activation of aflatoxin B1.
The mechanism by which vitamin A prevents or delays in chemical carcinogenesis remains unclear. In the present study, we assess the suggestive role of vitamin A in the initiation phase of carcinogenesis. We have conducted a dose-effect relationship between vitamin A dietary intake and aflatoxin B1 (AFB1) genotoxicity measured both in vitro and in vivo. Thus AFB1-induced mutagenesis in Salmonella typhimurium TA98 was investigated and compared to AFB1-induced single-strand breaks (SSBs) in DNA of rat hepatocytes. Rats were fed ad libitum with diet containing 0, 5, 50 or 500 IU of retinyl palmitate for 8 weeks. The AFB1-treated rats were injected i.p. with 1 mg/kg body weight. In the Ames test conditions TA98 back-reversion was negatively correlated with the log of vitamin A concentration in liver S9 fractions from experimental groups. However, the activities of metabolizing enzymes which specifically activate or deactivate AFB1 were found to be significantly decreased in vitamin A-deficient animals and weakly modified in vitamin A-supplemented animals. For in vivo experiments, the DNA elution rate of both AFB1-treated and untreated rats was increased in vitamin A deficiency condition (+79% and +17% respectively) and was reduced with the higher vitamin A dietary level (-44% and -53% respectively). DNA damage measured in vivo showed a significant positive correlation with mutagenic activity measured in the Ames test. These results confirm that the vitamin A status of animals can influence AFB1 genotoxic activity in vitro and indicate that this phenomenon also occurs in vivo. Thus a similar mechanism may be considered for the protective action of vitamin A both in vitro and in vivo. However, this mechanism is unlikely to involve modulation of the microsomal enzyme system responsible for AFB1 metabolism. Therefore a protective mechanism at the cytosolic or nuclear levels may be suggested.
Decoudu
S
S
Laboratoire de Toxicologie Alimentaire, Université de Bordeaux I, Réseau de Toxicologie Nutritionnelle MRES, Talence, France.
Cassand
P
P
Daubèze
M
M
Frayssinet
C
C
Narbonne
J F
JF
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004249:DNA Damage; D004032:Diet; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D016296:Mutagenesis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
D014801:Vitamin A; D016604:Aflatoxin B1; D005978:Glutathione