ABSTRACT
The purpose of this review is to present information about the role of activation of aflatoxins and other mycotoxins, of the aryl hydrocarbon receptor (AhR) pathway. Aflatoxins and other mycotoxins are a diverse group of secondary metabolites that can be contaminants in a broad range of agricultural products and feeds. Some species of Aspergillus, Alternaria, Penicilium, and Fusarium are major producers of mycotoxins, some of which are toxic and carcinogenic. Several aflatoxins are planar molecules that can activate the AhR. AhR participates in the detoxification of several xenobiotic substances and activates phase I and phase II detoxification pathways. But it is important to recognize that AhR activation also affects differentiation, cell adhesion, proliferation, and immune response among others. Any examination of the effects of aflatoxins and other toxins that act as activators to AhR must consider the potential of the disruption of several cellular functions in order to extend the perception thus far about the toxic and carcinogenic effects of these toxins. There have been no Reviews of existing data between the relation of AhR and aflatoxins and this one attempts to give information precisely about this dichotomy.
ABSTRACT
The identification of aflatoxins as human carcinogens has stimulated extensive research efforts, which continue to the present, to assess potential health hazards resulting from contamination of the human food supply and to minimize exposure. The use of biomarkers that are mechanistically supported by toxicological studies will be important tools for identifying stages in the progression of development of the health effects of environmental agents. miRNAs are small non-coding mRNAs that regulate post-transcriptional gene expression. Also, they are molecular markers of cellular responses to various chemical agents. Growing evidence has demonstrated that environmental chemicals can induce changes in miRNA expression. miRNAs are good biomarkers because they are well defined, chemically uniform, restricted to a manageable number of species, and stable in cells and in the circulation. miRNAs have been used as serological markers of HCC and other tumors. The expression patterns of different miRNAs can distinguish among HCC-hepatitis viruses related, HCC cirrhosis-derivate, and HCC unrelated to either of them. The main objective of this review is to find unreported miRNAs in HCC related to other causes, so that they can be used as specific molecular biomarkers in populations exposed to aflatoxins and as early markers of exposure, damage/presence of HCC. Until today specific miRNAs as markers for aflatoxins-exposure and their reliability are currently lacking. Based on their elucidated mechanisms of action, potential miRNAs that could serve as possible markers of HCC by exposure to aflatoxins are miR-27a, miR-27b, miR-122, miR-148, miR-155, miR-192, miR-214, miR-221, miR-429, and miR-500. Future validation for all of these miRNAs will be needed to assess their prognostic significance and confirm their relationship with the induction of HCC due to aflatoxin exposure.
