Caffeine potentiates the formation of micronuclei caused by environmental chemical carcinogens in V79 Chinese hamster cells.
The effect of caffeine on the genotoxicity of several carcinogenic compounds representing various classes of chemicals was investigated in a panel of V79 Chinese hamster cells genetically engineered to express cytochromes P4501A1 and P4501A2 and differing in their expression of N-acetyltransferases. The formation of micronuclei served as genetic endpoint. The results show that caffeine increases the number of micronuclei induced by 2-aminoanthracene several fold in the test cell lines. The lowest concentration of caffeine enhancing 2-aminoanthracene-induced genotoxicity was 100 nM. Caffeine also potentiated the genotoxicity of aflatoxin B1, 2-amino-3-methylimidazo[4,5-f]-quinoline. N-methyl-N-nitro-N-nitrosoguanidine, 1,6-dinitropyrene, and 7,8-diol-benzo[a]pyrene. Overall, caffeine lowered the effective genotoxic concentrations of these agents by a factor of about three. In contrast, the genotoxic effect of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone is markedly decreased in the presence of caffeine. The results indicate that caffeine may modulate the genotoxicity of chemical carcinogens by different mechanisms.
Kiefer
F
F
GSF-National Research Center for Environment and Health, Neuherberg, Germany.
Wiebel
F J
FJ
D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D002110:Caffeine / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity; D009602:Nitrosamines / Q000633:toxicity; D011721:Pyrenes / Q000633:toxicity; D011804:Quinolines / Q000633:toxicity
D000873:Anthracenes; D002274:Carcinogens, Environmental; D009153:Mutagens; D009602:Nitrosamines; D011721:Pyrenes; D011804:Quinolines; D008769:Methylnitronitrosoguanidine; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D002110:Caffeine; C033309:1,6-dinitropyrene; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C006593:2-anthramine; D016604:Aflatoxin B1; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2