EFFECT OF AGING AND INTERVAL BETWEEN PRIMARY AND SECONDARY-TREATMENT IN CARCINOGENESIS INDUCED BY NEONATAL EXPOSURE TO 5-BROMODEOXYURIDINE AND SUBSEQUENT ADMINISTRATION OF N-NITROSOMETHYLUREA IN RATS

LIO rats were exposed to s.c. injections (3.2 mg) of a synthetic analogue of thymidine, 5-bromo-2'-deoxyuridine (BrdUrd) on the 1st, 3rd, 7th and 21st days of life and at the age of 3 or 15 months they were i.v. injected with N-nitrosomethylurea (NMU) at a single dose of 10 or 50 mg/kg or with solvent. It was shown that early neonatal exposure to BrdUrd was followed by the increase in the incidence of tumor development and by the decrease of their latency. The carcinogenic effect of NMU alone correlated with the dose of the carcinogen in 3-month-old rats and did not correlate with dose in the 15-month-old ones. As compared to the 3-month-old rats, the incidence of total and malignant tumors and tumors of some localization was decreased in the elder ones, but survival of tumor-bearing rats was decreased in the elder group as compared to the younger one. These data suggests the age-related decrease in both the carcinogenic effect of NMU and in the number of events which are necessary for a tumor development. The exposure to BrdUrd was followed by the increase in the susceptibility of rats to subsequent carcinogenic effect of NMU injected at the doses of 10 or 50 mg/kg into 3- and 15-month-old rats, mostly to the tissues being target to NMU. Our data have demonstrated that the exposure to BrdUrd in the early life was followed by the irreversible initiating effect which persists over a long time in a several tissues.