Genotoxicity of ochratoxin A by Salmonella mutagenicity test after bioactivation by mouse kidney microsomes.
Ochratoxin A (OTA) was, up to now, believed to be non-mutagenic in the classical Salmonella typhimurium reverse mutation test. This was confirmed using rat liver microsomal fractions with the strains, TA1535, TA1538 and TA98, and up to 1210 micrograms/plate, utilizing an Ames microtest. However, using mice kidney microsomal fractions as metabolic activators, reverse mutations were obtained with the three strains used, in the presence of either NADP or arachidonic acid as cofactors. The mutagenicity was higher with arachidonic acid than with NADP using the TA1535 strain. This lends support to the results concerning the DNA or dGMP adducts obtained in vitro which were also higher in the presence of arachidonic acid, and indicate that several metabolic pathways of OTA can lead to genotoxic compounds. In addition, both base pair substitutions and frameshift mutations can be caused by OTA after metabolic activation.
Obrecht-Pflumio
S
S
Laboratoire de Biologie Végétale Appliquée, IUT Louis Pasteur, Schiltigheim, France.
Chassat
T
T
Dirheimer
G
G
Marzin
D
D
D000818:Animals; D016718:Arachidonic Acid / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009183:Mycotoxins / Q000378:metabolism / Q000633:toxicity*; D009249:NADP / Q000494:pharmacology; D009793:Ochratoxins / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D013045:Species Specificity
D002273:Carcinogens; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A; D016718:Arachidonic Acid; D009249:NADP