USPHS, and by Contract AT (30-1), 910 from the United States

We have previously reported that 7,12-dimethylbenz(a)an thracene (DMBA), given i.v. 24 hr after partial hepatectomy when DNA replication is maximal, binds tightly to DNA, inhibits its synthesis, and induces neoplastic changes in regenerating rat liver. We now report that DMBA injected i.v. 5 hr after partial hepatectomy (i.e., during the early prereplicative phase) inhibits DNA synthesis for at least 48 hr. The amount of tritiated DMBA bound to DNA by 11 hr equals the maximum amount found in intact rat liver; however, from 11 to 24 hr the amount bound to DNA increases 2to 3-fold (in untreated regenerating rat liver, DNA synthesis begins 16 hr after partial hepatectomy). In the small intestine, in which DNA synthesis is continuous and relatively constant in rate, the amount of DMBA bound to DNA is maximal by I 1 hr. The amount of DNA.bound benz(a)anthracene given i.v. 5 hr after partial hepatectomy decreases from 11 to 24 hr. Binding of DMBA in regenerating rat liver persists for at least 4 weeks; in small intestine the amount of DNA-bound carcinogen decreases at a rate suggesting loss by cell renewal. It appears that, on entry into the replicative phase, DNA becomes more susceptible to binding and the bound carcinogen persists in surviving cells.