title: Hypomethylation as a cause of homocysteine-induced cell damage in human cell lines.
abstract: Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. In the present study we have investigated the possible role of hypomethylation as a cause of homocysteine-induced cell damage in two human cell lines. A significant growth retardation was observed in HeLa cell cultures in the combined presence of homocysteine and adenosine, but first at concentrations of 250 micromol/l of each. A significant decrease of intracellular glutathione concentration was noted both in the presence of homocysteine (250 micromol/l) alone and in the presence of the combination of homocysteine and adenosine (250 micromol/l). Intracellular concentration of homocysteine was increased to a similar extent both in the presence of homocysteine alone and in the presence of a combination of homocysteine and adenosine. Similar findings to those described for HeLa cell cultures were observed in endothelial cell cultures. Furthermore, in the presence of copper ions together with 100 micromol/l of adenosine and homocysteine a significantly retarded cell growth was observed in HeLa cell cultures. This finding shows that a combination of two potentially cell-damaging mechanisms (formation of oxygen radicals and hypomethylation) aggravated the retardation of cell growth compared to only one of these mechanisms being present. Thus, it is likely that several mechanisms of homocysteine-induced cell damage contribute to the increased rate of the atherogenic process observed in hyperhomocysteinemia.
authors.affiliation: Department of Clinical Chemistry, Institute for Laboratory Medicine, University Hospital, Lund, Sweden. bjorn.hultberg@klinkem.lu.se
authors.forename: B
authors.initials: B
authors.lastname: Hultberg
authors.forename: A
authors.initials: A
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Isaksson
mesh_terms: D000241:Adenosine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006710:Homocysteine / Q000633:toxicity*; D006801:Humans; D009186:Myelin Sheath / Q000473:pathology*; D011506:Proteins / Q000378:metabolism
chemical_list: D011506:Proteins; D006710:Homocysteine; D005978:Glutathione; D000241:Adenosine