The effects of the mycotoxin austdiol on cell cycle progression, cytotoxicity and genotoxicity in Chinese hamster ovary (CHO-K1) cells

Abstract

Austdiol is a mycotoxin mainly produced byAspergillus ustus andMycoleptodiscus indicus. These fungi are found in rye, oats, barley, corn and feed grains; thus, as a potential contaminant of human food and animal feed, this mycotoxin is of great concern. As such, the elucidation of the cytotoxicity and mutagenicity of austdiol is important. In this study, austdiol was purified from a rice-oat solid medium culture ofM. indicus using chromatographic separation techniques. Chinese hamster ovary (CHO-K1) cells were then used to study the effect of austdiol on mammalian cell cycle, clonogenicity and DNA damage. Austdiol induced cell cycle arrest in G2/M phase, with a decreased S phase population and increased sub-G1 population. Austdiol also increased the polyploid population. These events resulted in cell death detected 7 days after treatment by clonogenic assay. DNA damage represents the main mechanism of action of austdiol, which induces DNA breaks and increases the frequency of micronuclei and nucleoplasmic bridges in binucleated cells in a CHO-K1 cell line. Moreover, cells exposed to austdiol and doxorubicin (DXR) combined treatments presented a reduced number of colonies and increased frequencies of micronuclei and nucleoplasmic bridges compared with negative control and cells treated with austdiol or DXR alone.