Lefevre P A, Ashby J
ICI Central Toxicology Laboratory, Cheshire, UK.
Carcinogenesis. 1989 Jun;10(6):1067-72. doi: 10.1093/carcin/10.6.1067.
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.
已使用B6C3F1小鼠评估了小鼠肝癌致癌物二氯甲烷（DCM）诱导肝细胞分裂的潜力（通过DNA合成增加来监测），DCM在该品系小鼠中具有致癌性，但显然没有基因毒性。雄性小鼠通过经口灌胃给予玉米油中的DCM（1000毫克/千克）或吸入含4000 ppm DCM的空气2小时来接触DCM。在处死前，通过每小时连续4次腹腔注射氚标记的胸腺嘧啶核苷，对进行DNA合成（S期）的细胞进行放射性标记。在灌胃研究中未观察到S期活性的证据。吸入研究导致S期发生率有一些微弱但具有统计学意义的增加，但由于在一些对照组中也观察到类似的增加，其生物学意义尚不清楚。结论是，DCM不具有三氯乙烯、多溴联苯和四氯化碳等假定的非基因毒性小鼠肝癌致癌物的促有丝分裂特性，因此其对小鼠肝脏的致癌性在机制上仍然不明。
