Comparative study of diethylnitrosamine-initiated two-stage hepatocarcinogenesis in C3H, C57BL and BALB mice promoted by various hepatopromoters.

The comparative inducibility of enzyme-altered islands (EAIs) by diethylnitrosamine (DEN) and their responsiveness to hepatopromoters belonging to different classes were studied in C3H/HeN (C3H), C57BL/6N (C57) and BALB/cA (BALB) mice. Male mice were given an i.p. injection of DEN (20 micrograms/g body weight) after partial hepatectomy at 6 weeks of age and then fed either basal diet or diet containing phenobarbital (PB) (500 p.p.m.), clofibrate (CF) (1000 p.p.m.) or ethynyl estradiol (EE) (10 p.p.m.). The numbers and size distribution of EAIs were assessed after the mice were killed at week 20, utilizing stereological methods. In the groups receiving DEN but no promoter, the number and mean size of the lesions were far larger in the C3H mice than in the other strains. Under the promoting pressure of PB, the growth of EAIs in C3H and BALB were accelerated remarkably, but those of C57 mice only slightly. Interestingly, in BALB the number of EAIs was much fewer than those of C3H in spite of their good sensitivity to PB, suggesting that BALB was refractory to the initiation process by DEN. A promoting effect for CF could only be demonstrated for the C3H strain and EE as the dose used inhibited the development of EAIs in all the strains. The experimental data thus indicate that interstrain differences in two-stage hepatocarcinogenesis among mice with different genetical backgrounds may exist, either in initiation or promotion, or in both processes.