RESUMO
Fumonisin B(1) (FB(1)), a widespread Fusarium toxin which is frequently found in corn, causes liver tumors in laboratory rodents and is a suspected human carcinogen. The compound was tested in micronucleus (MN) and single cell gel electrophoresis (SCGE) assays in human derived hepatoma (HepG2) cells and caused a pronounced dose-dependent genotoxic effect at exposure concentrations > or = 25 microg/ml. In contrast, no induction of his(+) revertants was found in Salmonella microsome assays with strains TA98, TA100, TA102, TA1535 and TA1537 upon addition of HepG2-derived enzyme (S9) mix in liquid incubation assays with identical exposure concentrations. Taken together, our results indicate that FB(1) is clastogenic in human derived cells. This observation supports the assumption that this compound may act as a genotoxic carcinogen in humans.
Assuntos
Carcinógenos Ambientais , Carcinoma Hepatocelular/metabolismo , Fumonisinas , Mutagênicos , Ensaio Cometa , Relação Dose-Resposta a Droga , Humanos , Cinética , Testes para Micronúcleos , Modelos Químicos , Fatores de Tempo , Células Tumorais CultivadasRESUMO
The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef ('beef mix') and chicken ('chicken mix'). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with a high consumption of LB-containing foods.