Modulation of genetic resistance to hepatocarcinogenesis in DRH rats by partial hepatectomy

The DRH is an inbred rat strain highly resistant to chemically induced hepatocarcinogenesis. Two clusters of resistance loci Drh1 and Drh2 on chromosome 1 and 4 yield strong resistance to the formation of enzyme-altered foci and their progression. To evaluate the effect of enhanced cell proliferation in the progression stage, a partial hepatectomy (PH) was carried out in (DRH x F344)F1 rats 8 weeks after the start of 3'-Me-DAB administration. The incidence of liver cancer in the PH-F1 rats was equivalent to that in the F344 rats, although the number of tumors per rat was much lower. In contrast, the F1 rats without PH rarely developed cancers. Such modulation was not due to the loss of the resistance allele, since none of 18 hepatocellular carcinomas in PH-F1 rats showed allelic imbalance at Drhl and Drh2.