Carcinogenesis induced by neonatal exposure to various doses of 5-bromo-2'-deoxyuridine in rats

Male and female outbred LIO rats were exposed to subcutaneous injections of 3.2 mg 5-bromo-2'-deoxyuridine (BrdUrd), on day 1; days 1 and 3; or days 1, 3, 7, and 21 following birth. The mean life-span decreased by 40.9, 31.2 and 38.9% in males exposed to 1, 2 or 4 injections of BrdUrd, respectively, and by 22.9, 10.5 and 23.4% in females, respectively, compared to the controls. The agent increased the population aging rate of the exposed male and female rats. Total tumor incidences in males exposed to 0, 3.2, 6.4 or 12.8 mg of BrdUrd were 21.1, 27.3, 40.0 and 33%, respectively, and in the females 44.3, 54.5, 48.1 and 56.3%, respectively. Only the largest dose of BrdUrd significantly increased the tumor incidence in the exposed rats as compared to the control ones (P < 0.05). However, tumor latency was shorter in any group of rats exposed to BrdUrd, as compared to the control one. The exposure to 0, 1, 2 or 4 injections of BrdUrd was followed by the development of testicular Leydigomas in 0, 0, 28 and 12% of males, respectively. There was no organ or tissue target for BrdUrd in the females. However, the development of tumours not typical for the rats and the widening of tumor spectrum was observed in the female rats exposed to the agent.