Effects of S-adenosylhomocysteine and homocysteine on DNA damage and cell cytotoxicity in murine hepatic and microglia cell lines.
Limited research has been performed on S-adenosylhomocysteine (SAH) or homocysteine (Hcy)-evoked cell damage in hepatic and neuronal cells. In this study, we assessed effects of SAH or Hcy on cell cytotoxicity and DNA damage in hepatic and neuronal cells 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 h. The influences of SAH or Hcy on lipid peroxidation and DNA methylation were also measured in both cell lines. SAH (5-20 microM) 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, whereas Hcy caused minimal effects on these two parameters at much higher concentrations. 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, resulting in irreversible DNA damage and increased cell cytotoxicity. In addition, higher Hcy could induce cellular DNA damage through increased lipid peroxidation and DNA hypomethylation. We suggest that SAH is a better marker of cell damage than Hcy in hepatic and microglia cells.
Liu
Chia-Chyuan
CC
Department of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan.
Ho
Wen-Yueh
WY
Leu
Kuen-Lin
KL
Tsai
Hsin-Mao
HM
Yang
Tsai-Hsiu
TH
D000818:Animals; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D006710:Homocysteine / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D012435:S-Adenosylhomocysteine / Q000633:toxicity*; D013696:Temperature; D013778:Tetrazolium Salts / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D005562:Formazans; D013778:Tetrazolium Salts; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; C079782:MTT formazan; D012435:S-Adenosylhomocysteine