Effects of chronic exposure to microcystin-LR on hepatocyte mitochondrial DNA replication in mice

Microcystins (MCs) are produced by cyanobacterial blooms, and microcystin-LR (MC-LR) is the most toxic among the 80 MC variants. Data have shown that the liver is one of the specific target organs for MC-LR, which can cause mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. However, the underlying mechanism is still unclear. In the present study, we evaluated the genetic toxicity of MC-LR in mice drinking water at different concentrations (1, 5, 10, 20, and 40 μg/L) for 12 months. Our results showed that long-term and persistent exposure to MC-LR increased the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels of DNA in liver cells, damaged the integrity of mtDNA and nuclear DNA (nDNA), and altered the mtDNA content. Notably, MC-LR exposure can change the expression of mitochondrial genes and nuclear genes that are critical for regulating mtDNA replication and repairing oxidized DNA. They also further impaired the function of mitochondria and liver cells.