3 years ago

Microcystin-LR increases genotoxicity induced by aflatoxin B1 through oxidative stress and DNA base excision repair genes in human hepatic cell lines

Microcystin-LR increases genotoxicity induced by aflatoxin B1 through oxidative stress and DNA base excision repair genes in human hepatic cell lines
Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) simultaneously exist in polluted food and water in humid and warm areas, and each has been reported to be genotoxic to liver and associated with hepatocellular carcinoma (HCC). However, the genotoxic effects of the two biotoxins in combination and potential mechanism remain unknown. We treated the human hepatic cell line HL7702 with AFB1 and MC-LR together at different ratios, examined their genotoxic effects using micronuclei and comet assays, and evaluated the possible mechanism by measuring oxidative stress markers and DNA base excision repair (BER) genes. Our data show that co-exposure to AFB1 and MC-LR significantly increased DNA damage compared with AFB1 or MC-LR alone as measured by the levels of both micronuclei and tail DNA. Meanwhile, AFB1 and MC-LR co-exposure showed biphasic effects on ROS production, and a gradual trend towards increased Glutathione (GSH) levels and activity of Catalase (CAT) and Superoxide Dismutase (SOD). Furthermore, MC-LR, with or without AFB1, significantly down-regulated the expression of the base excision repair (BER) genes 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross complementing group 1 (XRCC1). AFB1 and MC-LR in combination upregulated the expression of the BER gene apurinic/apyrimidinic endonuclease 1 (APE1), whereas either agent alone had no effect. In conclusion, our studies show that MC-LR exacerbates AFB1-induced genotoxicity and we report for the first time that this occurs through effects on oxidative stress and the deregulation of DNA base excision repair genes.

Publisher URL: www.sciencedirect.com/science

DOI: S0269749116325830

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.