Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin.
Mycotoxins are fungal secondary metabolites with very diversified toxic effects in humans and animals. In the present study, patulin (PAT) and citrinin (CTN), two prevalent mycotoxins, were evaluated for their genotoxic effects and oxidative damage to mammalian cells, including Chinese hamster ovary cells (CHO-K1), human peripheral blood lymphocytes, and human embryonic kidney cells (HEK293). PAT, but not CTN, caused a significant dose-dependent increase in sister chromatid exchange (SCE) frequency in both CHO-K1 and human lymphocytes. PAT also elevated the levels of DNA gap and break in treated CHO-K1. In the single cell gel electrophoresis (SCGE) assay, exposure of HEK293 to concentrations above 15 microM of PAT induced DNA strand breaks; the tail moment values also greatly increased after posttreatment with formamidopyrimidine-DNA glycosylase (Fpg). This suggests that in human cells PAT is a potent clastogen with the ability to cause oxidative damage to DNA. However, no significant change in the tail moment values in CTN-treated cultures was found, suggesting that CTN is not genotoxic to HEK293. Incubation of HEK293 with CTN increased the mRNA level of heat shock protein 70 (HSP70), but not that of human 8-hydroxyguanine DNA glycosylase 1 (hOGG1). PAT treatment did not modulate the expression of either HSP70 or hOGG1 mRNA.
D000818:Animals; D016466:CHO Cells; D002953:Citrinin / Q000378:metabolism / Q000633:toxicity*; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009183:Mycotoxins / Q000378:metabolism / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D010365:Patulin / Q000378:metabolism / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D018840:HSP70 Heat-Shock Proteins; D009153:Mutagens; D009183:Mycotoxins; D002953:Citrinin; D010365:Patulin; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase