Liver Regeneration and Induction of Hepatomas in B6AF1 Mice by Urethan

TLDR: The pattern of regeneration and cell proliferation was studied in liver remnants of B6AF1 hybrid mice during the first 85 hr following partial hepatectomy, and the hepatoma incidence showed a clear-cut relationship between the timing of urethan treatment in relation to prior hepATEctomy.

Abstract: The pattern of regeneration and cell proliferation was studied in liver remnants of B6AF1 hybrid mice during the first 85 hr following partial hepatectomy. On the basis of the estimated timing of DNA synthesis and mitoses, male and female adult mice were inoculated once with urethan, 1 mg/g body weight, at the following times after partial hepatectomy: 4 to 5 hr, i.e., at an early prereplicative period; 17 to 18 hr, during a late prereplicative period; 31 to 33 hr, shortly before the onset of extensive DNA duplication; and 46 hr, before the peak of mitoses. The hepatoma incidence showed a clear-cut relationship between the timing of urethan treatment in relation to prior hepatectomy. After 13 months, 10, 68, 42, and 77% of the male animals bore at least one hepatoma, compared with 3.3% among untreated males, 6% in those treated only with urethan, and 19.4% following hepatectomy alone. Hepatic tumors were rare in the females. In urethan-treated mice, body weight was reduced by up to 50% of that of controls.