Age- and sex-associated diethylnitrosamine dealkylation activity of the mouse liver and hepatocarcinogenesis.

In order to evaluate the possible implication of the enzymatic competence of liver in the carcinogenesis by diethylnitrosamine, we assayed liver homogenates from 1-, 7-, 15-, 28-, 42-, and 70-day-old C57BLX C3H F! mice of both sexes for dealkylating activity. These studies were comple mented by a series of carcinogenesis bioassays in which 15and 42-day-old mice of the same strain were administered diethylnitrosamine i.p. (10 jig/g body weight, once). Groups of mice were killed at 56 and 66 weeks of age, and the incidence of liver tumors was assessed. The results indicated that enzymatic competence was already present in newborn animals and that, henceforth it increased and reached peak activity in both sexes at between the 7th and 15th day of age; at those ages, no difference between the sexes was observed. Thereafter, enzymatic activity decreased with age in both sexes but decreased more rapidly in females. This resulted in a statistically significant sex difference beginning with the 28th day of life. Carcinogenesis bioassay series showed a significantly higher incidence of liver tumors in mice treated at Day 15 than in those treated when 6 weeks of age. The sex difference in the incidence of liver tumors which was observed at week 56 disappeared by the 66th week of life in animals treated with diethylnitrosamine as infants, indicating the same degree of inception of carcinogenesis for both sexes and a slower rate of neoplastic expression for females. The positive correlation between degree of diethylnitro samine dealkylation and hepatocarcinogenesis suggested their causal relationship without excluding the role of other age-associated factors.