Correlation between time of partial hepatectomy after a single treatment with diethylnitrosamine and induction of adenosinetriphosphatase-deficient islands in rat liver.

Full-grown Sprague-Dawley rats were given a single i.p. injection of diethylnitrosamine (80 mg/kg) and subjected to partial hepatectomy at various times from 4 hr to 7 days later to induce semisynchronized liver cell proliferation. Then, they were maintained on basal diet containing 0.05% phenobarbital, which is known to promote hepatocarcinogenesis, for 16 weeks. By this method, significant numbers of adenosinetriphosphatase-deficient islands were induced in the liver. These islands are considered to be formed by immediate progeny of "initiated cells" or cell precursors in hepatocarcinogenesis, and they can be used as a marker of carcinogenic activity. Results showed that the number of enzyme-altered islands induced was inversely proportional to the time between carcinogen treatment and subsequent partial hepatectomy. The incidence of enzyme-altered islands was greatest when the two treatments were separated by 4 hr and decreased when they were separated by 7 days. These data suggest that carcinogen-induced DNA damage, if not repaired before cell proliferation, is intimately related to the initiation-fixation process of carcinogenesis.