Comparative studies on cytotoxic and genotoxic effects of two 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 vitro for 1 h with methylmercury chloride (MMC, 0.5-4 micrograms/ml) and dimethylmercury (DMM, 5-40 micrograms/ml). The cytotoxicity of the two organic mercury compounds was assessed by dye exclusion, and the extent of induced DNA fragmentation was measured with a single-cell microgel electrophoresis 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 causing a significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatocytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 micrograms/ml MMC was carried out in human lymphocytes obtained from an adult male donor. The bulk of DNA repair occurred 90 min after in vitro exposure, and it was about complete by 120 min following cessation of exposure. Finally, in order to have a basis for extrapolating to the human situation, in vivo studies were performed with Sprague-Dawley rats, also assessing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directly compared to the in vitro data obtained in the same cells.
Betti
C
C
Institute for Hygiene and Toxicology, Federal Research Center for Nutrition, Karlsruhe, Germany.
Barale
R
R
Pool-Zobel
B L
BL
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004249:DNA Damage; D005753:Gastric Mucosa / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D008767:Methylmercury Compounds; D009153:Mutagens; C073972:dimethyl mercury; C004925:methylmercuric chloride