Co-exposure to Ochratoxin A and Sterigmatocystin: in vitro assessment of mycotoxin's effects on hepatocellular carcinoma

摘要

Background: The increased international awareness on mycotoxin hazards indicates the possible negative impact on Public Health of certain mycotoxin combinations. However, minor attention is given on the effects resulting from chronic exposure to low amounts of mycotoxin mixtures. Aims: To examine apoptotic and cytogenetic effects of two common environmental contaminants that share hepatoxic and carcinogenic properties. These are Ochratoxin A (OTA) and Sterigmatocystin (STER) applied alone or in combination at sub-toxic concentrations on the human hepatoceiiular cancer cell line Hep3B. Methods: Caspase-3 activity was used as an apoptotic marker. MTT assay and mitotic index (MI) were used as cancer cell viability and cytotoxicity endpoints. The Sister Chromatid Exchange (SCEs) methodology was applied to assess possible genotoxic activity. Results: Single STER dosage reduced MI and MTT activity of Hep3B, exhibiting cell toxicity in concentrations 10-12 -10-6 M, while single STER and OTA administration enhanced caspase-3 activity. Co-administration of STER-OTA reversed the effects of single agents on MI, MTT and caspase-3 at concentrations ＜10-8 M. Finally, both mycotoxins, alone and in combination, significantly increased SCE ratio of Hep3B. Conclusions: Hep3B exposure to sub-toxic levels of STER exerted a significant apoptotic and cytogenetic potential. Co-treatment with OTA-STER reversed all but genotoxic actions. Apparently, in vitro exposure to these toxins alone or in combination indicates effects that require further evaluation in order to illuminate possible hazardous outcomes on Public Health.