An Overview of the Mechanisms of Microcystin-LR Genotoxicity and Potential Carcinogenicity

Author(s): Bojana Zegura

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 16 , Issue 13 , 2016

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Microcystins (MCs) are hepatotoxic cyclic peptides, and microcystin-LR (MCLR) is one of the most abundant and toxic congeners. MCLR-induced hepatotoxicity occurs through specific inhibition of serine/threonine protein phosphatases 1 and 2A, which leads to hyperphosphorylation of many cellular proteins. This eventually results in cytoskeletal damage, loss of cell morphology, and the consequent cell death. It is generally accepted that inhibition of protein phosphatases is the main mechanism associated with the potential tumor-promoting activities of MCs. MCs can induce excessive formation of reactive oxygen and nitrogen species, which results in DNA damage. Although MCLR is not a bacterial mutagen, in mammalian cells it can induce mutations, as predominantly large deletions, and it has clastogenic actions. Although MCLR disrupts the mitotic spindle, its aneugenic activity has not been studied in detail. MCLR interferes with DNA damage repair processes, which contribute to genetic instability. Furthermore, MCLR increases expression of early response genes, including proto-oncogenes, and genes involved in responses to DNA damage and repair, cell-cycle arrest, and apoptosis. However, published data on the genotoxicity and carcinogenicity of MCs have been contradictory; therefore, the aim of this review is to provide current overview of the genotoxic and potential carcionogenic activities of MCs in bacteria and mammalian cells, with a focus on MCLR. The mechanisms of MC acute toxicity, their biochemical and morphological effects, and their effects on the cell cytoskeleton are covered in detail elsewhere in the literature, including in this Special Issue on “Cellular and biochemical effects of microcystins (cyanobacterial toxins) and their potential medical consequences”.

Keywords: Cyanotoxins, carcinogenic, DNA damage, genotoxic, microcystin-LR, tumor promotion.

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Article Details

Year: 2016
Published on: 08 March, 2016
Page: [1042 - 1062]
Pages: 21
DOI: 10.2174/1389557516666160308141549
Price: $65

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