The induction of chromosomal damage in rat hepatocytes and lymphocytes. I. Time-dependent changes of the clastogenic effects of diethylnitrosamine, dimethylnitrosamine and ethyl methanesulfonate.
Male Wistar rats received a single injection of diethylnitrosamine (DEN), dimethylnitrosamine (DMN) or ethyl methanesulfonate (EMS). After a number of time intervals (up to 56 days) liver cells were assayed for the presence of possible preclastogenic damage by performing partial hepatectomy and subsequent analysis of chromosomal damage (micronucleus formation) in isolated hepatocytes. Peripheral blood lymphocytes from the same animals were collected, stimulated to proliferate and assayed for the frequency of sister-chromatid exchanges (SCEs). Whereas all agents significantly increased frequencies of SCEs in lymphocytes up to at least 28 days (EMS) or 56 days (DMN, DEN) after injection, only the latter 2 compounds gave rise to significantly increased incidences of micronucleated hepatocytes. DMN-induced preclastogenic damage in hepatocytes was lost between 28 and 56 days after injection. After DEN, this type of damage was persistent over the entire experimental period (56 days). When rats treated with DEN did not undergo partial hepatectomy, the frequencies of micronuclei at different time intervals after treatment were at control level. This result, together with those from hepatectomized DEN-treated rats, suggests that it is the persistent character of the preclastogenic damage that is responsible for the occurrence of micronucleated hepatocytes at later time intervals after treatment with DEN, rather than the stability of micronuclei which might eventually have been formed soon after injection.
D000818:Animals; D002273:Carcinogens; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009602:Nitrosamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D002273:Carcinogens; D009602:Nitrosamines; D004052:Diethylnitrosamine; D005020:Ethyl Methanesulfonate; D004128:Dimethylnitrosamine