Abstract
Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin produced by toxicogenic Aspergillus species. AFB1 has been reported to cause serious adverse health effects, such as cancers and abnormal development and reproduction, in animals and humans. AFB1 is also a potent genotoxic mutagen that causes DNA damage in vitro and in vivo. However, the link between DNA damage and abnormal development and reproduction is unclear. To address this issue, we examined the DNA damage, germline apoptosis, growth, and reproductive toxicity following exposure to AFB1, using Caenorhabditis elegans as a study model. Results found that AFB1 induced DNA damage and germline apoptosis, and significantly inhibited growth and reproduction of the nematodes in a concentration-dependent manner. Exposure to AFB1 inhibited growth or reproduction more potently in the DNA repair-deficient xpa-1 nematodes than the wild-type N2 strain. According to the relative expression level of pathway-related genes measured by real-time PCR, the DNA damage response (DDR) pathway was found to be associated with AFB1-induced germline apoptosis, which further played an essential role in the dysfunction of growth and reproduction in C. elegans.
Highlights
Aflatoxins are the most studied group of mycotoxins produced by Aspergillus flavus and Aspergillus parasitics, which naturally present in a variety of animal feeds and human foods, in cereal grains, nuts, and feedstuffs [1]
Building on the previous findings, the present study investigated the toxic effects of Aflatoxin B1 (AFB1) on Building on the previous findings, the present study investigated the toxic effects of AFB1 growth and reproduction of C. elegans
The results presented in this study strongly support that the nucleotide excision repair system (NER) system is in charge of repairing the DNA damages caused by AFB1
Summary
Aflatoxins are the most studied group of mycotoxins produced by Aspergillus flavus and Aspergillus parasitics, which naturally present in a variety of animal feeds and human foods, in cereal grains, nuts, and feedstuffs [1]. Aflatoxin B1 (AFB1 ) is the most toxic and hepatocarcinogenic among the known mycotoxins [2]. AFB1 is mainly metabolized by cytochrome P450 enzymes into the genotoxic metabolite, 8,9-epoxide-AFB1 (AFBO). AFBO can bind to DNA and cause the formation of AFB1 -DNA adducts [5]. AFB1 -DNA adducts may block normal replication and transcription, thereby causing lesions in the double-stranded DNA. The DNA lesions can be repaired or removed by the nucleotide excision repair system (NER) [6]. If the lesion persists in the genome DNA, it can lead to mutagenesis and carcinogenesis
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