Mitomycin C induced genotoxic stress in endothelial cells is associated with differential expression of proinflammatory cytokines.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
M Yu SinitskyA V Ponasenko

Abstract

Mitomycin C (MMC) is an alkylating chemotherapy drug that causes DNA crosslinking resulting in transcription arrest and apoptosis. DNA crosslinking is a critical damage to DNA that can be caused not only by MMC and other antitumor drugs, but also by various environmental and anthropogenic endo- and exogenous agents. Mammalian cells exposed to alkylating mutagens are characterized by severe genotoxic stress. Somatic mutations and genotoxic stress may lead to endothelial dysfunction, which is the initial stage of atherosclerosis, a leading cause of morbidity and mortality worldwide. Here we studied DNA damage, protein secretion and gene expression of IL6 and IL8 in primary human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) in vitro exposed to 500 ng/mL MMC. We observed an increase in levels of cytogenetic damage (micronuclei, nucleoplasmic bridges and nuclear buds) in MMC-treated cells compared to control cells. After 6 h incubation with MMC, both HCAEC and HITAEC displayed a decrease in IL8 concentration and the mRNA level of IL6 and IL8 compared to control cells. Removal of MMC from cultures after 6 h followed by 24 h incubation of cells in complete growth media led to ...Continue Reading

Citations

Apr 17, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·M Yu SinitskyA V Ponasenko
Jul 10, 2021·Signal Transduction and Targeted Therapy·Ruixue Huang, Ping-Kun Zhou

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