COMPARATIVE-STUDIES ON CYTOTOXIC AND GENOTOXIC EFFECTS OF 2 ORGANIC MERCURY-COMPOUNDS IN LYMPHOCYTES AND GASTRIC-MUCOSA CELLS OF SPRAGUE-DAWLEY RATS

Human lymphocytes (HL) as well as lymphocytes (RL), hepatocytes (RH), and gastric mucosa cells (GM) of Sprague-Dawley rats were treated in v itro for 1 h with methylmercury chloride (MMC, 0.5-4 mug/ml) and dimet hylmercury (DMM, 5-40 mug/ml). The cytotoxicity of the two organic mer cury compounds was assessed by dye exclusion, and the extent of induce d DNA fragmentation was measured with a single-cell microgel electroph oresis assay. Both MMC and DMM induced DNA damage and cytotoxicity in a dose-related manner in HL, RL, and GM. MMC was more effective in cau sing o significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatoc ytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 mug/ml M MC was carried out in human lymphocytes obtained from an adult male do nor. The bulk of DNA repair occurred 90 min after in vitro exposure, a nd it was about complete by 120 min following cessation of exposure. F inally, in order to have a basis for extrapolating to the human situat ion, in vivo studies were performed with Sprague-Dawley rats, also ass essing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directl y compared to the in vitro data obtained in the same cells. (C) 1993 W iley-Liss, Inc.