Evaluation of dichloromethane as an inducer of DNA synthesis in the B6C3F1 mouse liver.
The potential of the mouse hepatocarcinogen dichloromethane (DCM) to induce hepatocellular division, as monitored by increased DNA synthesis, has been evaluated using B6C3F1 mice--the strain in which it is carcinogenic but not apparently genotoxic. Male mice were exposed to DCM either by oral gavage in corn oil (1000 mg/kg) or by inhalation of an atmosphere containing 4000 p.p.m. DCM for 2 h. Cells undergoing DNA synthesis (S-phase) were radiolabelled by means of four consecutive i.p. injections of tritiated thymidine at hourly intervals prior to killing. No evidence of S-phase activity was observed in the gavage studies. The inhalation studies resulted in some weak, but statistically significant increases in S-phase incidence, but the biological significance was unclear due to similar increases being observed in some control groups. It is concluded that DCM does not share the mitogenic properties of such presumed non-genotoxic mouse liver carcinogens as trichloroethylene, polybrominated biphenyls and carbon tetrachloride, and as such its carcinogenicity to the mouse liver remains mechanistically obscure.
Lefevre
P A
PA
ICI Central Toxicology Laboratory, Cheshire, UK.
Ashby
J
J
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008752:Methylene Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D012016:Reference Values
D006843:Hydrocarbons, Chlorinated; D008752:Methylene Chloride