The limited research has been performed regarding the s-adenosylhomocysteine (SAH) or homocysteine (Hcy)-evoked cell damage in hepatic and neuronal cells. In this study we assessed effects of SAH or Hcy in hepatic and neuronal cells on cell cytotoxicity and DNA damage, and attempted to find the underlying mechanism. Cell cytotoxicity and DNA damage were evaluated in murine hepatic cells (BNL CL.2 cell line) and microglia cells (BV-2 cell line) with SAH or Hcy treatment for 48 hours. The influences of SAH or Hcy on lipid peroxidation and DNA methylation were also measured in both cell lines. SAH (5-20 M) or Hcy (1-5 mM) dose dependently inhibited cell cytotoxicity and enhanced DNA damage in both types of cells. Furthermore, SAH treatment markedly increased intracellular SAH levels and DNA hypomethylation, the effect of SAH was much stronger than that of Hcy. The findings were also obtained that Hcy significantly induced lipid peroxidation, but not SAH. The present results show that SAH might cause cellular DNA damage in hepatic and microglia cells by DNA hypomethylation, further resulting in irreversible DNA damage and decrement of cell cytotoxicity. Additionally, higher Hcy could induce cellular DNA damage through increased lipid peroxidation and DNA hypomethylation. We suggest that SAH is more informative to cell damage than that of Hcy in hepatic and microglia cells.
