Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

Abstract

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

Antigenotoxic effect of melatonin against mercuric chloride in human peripheral blood lymphocytes

“…In our study, Hg treatment showed a significant enhancement in CAs. Silva- Pereira et al (2014) reported increases in CAs after Hg compound exposures to blood cells and HL-60 cells (an acute myeloid leukemia lineage). In corroboration of our data, increased cytogenetic damage and genotoxicity was observed in blood cultures (Bahia et al, 1999).…”

Methylmercury inhibits prolactin release in a cell line of pituitary origin

“…Although the pituitary gland has already been highlighted as a potential target of mercury accumulation ( 4 ), the effects of this metal on the regulation of hormonal release are unclear. Previous studies showed associations (both positive and negative) between serum PRL and mercury exposure ( 6 ). This dual effect may be explained by different interactions between mercury species (inorganic and organic) and PRL secretion by the pituitary gland, which is controlled by neurotransmitters such as dopamine.…”

In vitro analysis of thimerosal genotoxicity and cytotoxicity effect

“…3 Another important mechanism of mercury genotoxicity is its ability to produce free radicals that can cause DNA damage. 4 Based on previous research on thimerosal and its importance in vaccines, this study aimed to examine the potential cytotoxic and genotoxic effects of specific thimerosal concentrations on human peripheral blood lymphocyte culture. 5…”