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Oxidative stress and DNA interactions are not involved in Enniatin‐ and Beauvericin‐mediated apoptosis induction
Author(s) -
Dornetshuber Rita,
Heffeter Petra,
LemmensGruber Rosa,
Elbling Leonilla,
Marko Doris,
Micksche Michael,
Berger Walter
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800571
Subject(s) - beauvericin , cytotoxicity , dna damage , oxidative stress , reactive oxygen species , apoptosis , cytotoxic t cell , topoisomerase , chemistry , programmed cell death , dna repair , dna , biology , biochemistry , microbiology and biotechnology , in vitro , mycotoxin , food science
The fusariotoxins beauvericin (BEA) and the structurally related enniatins (ENN) are frequent contaminants of grain‐based food and feed. They exert potent cytotoxic activities based on apoptosis induction. Since it is known, that reactive oxygen species (ROS) and DNA damage lead to apoptotic cell death, this study aimed to clarify whether oxidative stress and DNA interactions are involved in ENN‐ and BEA‐induced cytotoxicity. Diverse cellular and molecular assays indicated that oxidative stress does not contribute to ENN‐ and BEA‐induced cytotoxicity. In contrast, both fusariotoxins were shown to exert moderate antioxidative activities. Moreover, only at high concentrations (>100 μM) both mycotoxins were found to intercalate substantially into dsDNA and to inhibit the catalytic activity of topoisomerase I and II. Furthermore, the potent cytotoxic activity of ENN and BEA was shown to be widely independent of cellular mismatch‐ and nucleotide excision repair pathways. Also the ataxia‐telangiectasia mutated (ATM) protein kinase, a well known DNA damage sensor, did not affect BEAs cytotoxic potential while in ENN‐induced cytotoxicity ATM had a detectable but not a major modulating influence. Together, our data suggest that ROS and DNA damage are not key factors in ENN‐ and BEA‐mediated cytotoxicity.