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The potency of carcinogenic agents in eliciting neoplastic lesions has long been a concern of investigators in the field of oncology. This paper describes a method, based on quantitative stereologic calculations, to estimate the relative potency of chemicals as initiating and/or promoting agents. The parameters defined in this paper are: (a) Initiation index = no. foci induced X liver-1 X [mmole/kg body weight]-1; and (b) Promotion index = Vf/Vc X mmol-1 X wk-1. These parameters have been calculated for a number of chemical agents, based both on data from this laboratory and others published in the literature. Neither parameter varied significantly with the dose of two different initiating agents used in this study. The range of promotion indices extended over more than eight orders of magnitude, whereas that of the initiation indices was much less variable. Such parameters may be useful as quantitative estimates of the potency of hepatocarcinogenic agents not only in rodents, but potentially in quantitative risk estimations in the human.

Rats accustomed to eating during the first 8h of a daily 12h dark period re-established about 80% of intact liver weight, protein and DNA within 4 days following partial hepatectomy; further increases were not observed. Liver thymidine kinase activity and thymidine incorporation into liver DNA exhibited marked daily oscillations during liver regeneration. Maximum values were observed near the end of the dark period both in intact growing rats and in rats partially hepatectomized 2h before the end of the dark period. The time of day of surgery affected thymidine kinase activity and thymidine incorporation into DNA at specific times following partial hepatectomy. This seriously affects the interpretation of reports of experiments where the time of day of killing has been held constant and time of surgery varied. Highly significant correlation coefficients were observed for thymidine incorporation before killing versus thymidine kinase activity at time of killing and for thymidine versus orotic acid incorporation into DNA of livers from rats partially hepatectomized 2h before the end of the dark period and killed at 12h intervals. Thymidylate phosphatase activity returned to the normal amount at a rate similar to that for liver protein. Thymidylate phosphatase did not affect the validity of the thymidine kinase assay. The relationship of [14C]orotic acid to [3H]thymidine incorporation into liver DNA varied with the time of day, with the age of the rat and during the regeneration of the liver.