title: Mycotoxins' activity at toxic and sub-toxic concentrations: differential cytotoxic and genotoxic effects of single and combined administration of sterigmatocystin, ochratoxin A and citrinin on the hepatocellular cancer cell line Hep3B.
abstract: Food safety organizations indicate the likelihood of constant human and animal exposure to mycotoxin mixtures as a possible negative public health impact. Risk assessment demonstrates that certain mycotoxins of Aspergillus and Penicillium spp. are toxic and hold a significant genotoxic efficacy at nanomolar concentrations. The aim of the current study was to investigate the potential cytogenetic effects of sterigmatocystin (STER), ochratoxin A (OTA) and citrinin (CTN) alone or in combination, at pM to μΜ concentrations, on the human hepatocellular cancer cell line Hep3B. MTT reduction, mitotic divisions, cell cycle delays and sister chromatid exchange rates (SCE) were determined as endpoints of metabolic activity, cytotoxicity, cytostaticity, and genotoxicity, respectively. All mycotoxin treatments induce SCE rates from 10-12 M, while their cytotoxic and cytostatic potential varies. In PRI and MI assays, but not at MTT, STER alone or in combination with OTA + CTN appeared cytostatic and cytotoxic, even at 10-12 M, while CTN alone and all other combinations displayed substantial cellular survival inhibition in doses ≥ 10-8 M. Co-administration of STER + OTA or STER + CTN in concentrations ≤ 10-1 M, increased the MI and MTT activity, while it did not affect the PRI. Mycotoxin co-treatments revealed in general similar-to-additive or antagonistic genotoxic and cytotoxic effects. Our results for the first time describe that STER alone or in combination with OTA and/or CTN share a cytotoxic and cytogenetic potential even at picoMolar concentrations on human hepatoma cells in vitro.
authors: Cell Culture Unit, Laboratory of Experimental Surgery and Surgical Research, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece. nianninou9@gmail.com.
authors: Nikolia
authors: N
authors: Anninou
authors: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece. achatzak@med.duth.gr.
authors: Ekaterini
authors: E
authors: Chatzaki
authors: Cell Culture Unit, Laboratory of Experimental Surgery and Surgical Research, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece. fpapachr@med.duth.gr.
authors: Fotini
authors: F
authors: Papachristou
authors: Surgical Department, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece. mpitiak@med.duth.gr.
authors: Muichail
authors: M
authors: Pitiakoudis
authors: Cell Culture Unit, Laboratory of Experimental Surgery and Surgical Research, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece. mpitiak@med.duth.gr.
authors: Constantinos
authors: C
authors: Simopoulos
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002953:Citrinin / Q000633:toxicity*; D006801:Humans; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009793:Ochratoxins / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013241:Sterigmatocystin / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D009793:Ochratoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; D013241:Sterigmatocystin; C025589:ochratoxin A; D002953:Citrinin; C022616:thiazolyl blue