Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers.
The effects of several carotenoids of vitamin A and of 3-methylcholanthrene have been tested on the initiation of hepatocarcinogenesis by aflatoxin B1, using the sequential protocol of Solt and Farber. AFB1-induced DNA single-strand breaks and AFB1-metabolism were also assessed. The P4501A inducer carotenoids (canthaxanthin, astaxanthin, beta-apo-8'-carotenal) and 3-methylcholanthrene reduce the carcinogenicity of AFB1, divert AFB1-metabolism into the less genotoxic aflatoxin M1 and reduce AFB1-induced DNA single-strand breaks: we conclude that these carotenoids exert their protective effect through the deviation of AFB1 metabolism towards detoxification pathways. beta-Carotene decreased AFB1 carcinogenicity but did not alter its metabolism, probably acting by other mechanisms.
Gradelet
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Unité de Toxicologie Nutritionnelle, INRA, Dijon, France.
Astorg
P
P
Le Bon
A M
AM
Bergès
R
R
Suschetet
M
M
D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D002338:Carotenoids / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004032:Diet; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D014801:Vitamin A; D002338:Carotenoids; D008748:Methylcholanthrene; D016604:Aflatoxin B1