Failure of mitogen-induced cell proliferation to achieve initiation of rat liver carcinogenesis.

Experiments were designed to determine whether mitogen-induced cell proliferation is as effective as regenerative cell proliferation in achieving initiation of liver carcinogenesis. To test this hypothesis male Wistar rats were injected with a single dose of diethylnitrosamine (DENA) or N-methyl-N-nitrosourea (MNU) during the peak of DNA synthesis following the administration of the liver mitogen, lead nitrate, after partial hepatectomy (PH) or a necrogenic dose of CCl4. The initiated hepatocytes were monitored as gamma-glutamyltransferase (GGT)-positive foci using a 2-week selection regimen consisting of 0.03% 2-acetylaminofluorene (2-AAF) coupled with a necrogenic dose of CCl4. The results indicate that unlike compensatory cell proliferation such as that induced by PH or CCl4, mitogen-induced cell proliferation did not result in any initiated hepatocytes despite the fact that in both types of models the extent of liver cell proliferation at the time of the administration of the carcinogen is similar.