CARCINOGENESIS INDUCED BY COMBINED NEONATAL EXPOSURE TO 5-BROMO-2'-DEOXYURIDINE AND SUBSEQUENT TOTAL-BODY X-RAY-IRRADIATION IN RATS

Outbred LIO rats at 1, 3, 7 and 21 days of postnatal life were exposed to s.c. injections of 3.2 mg of 5-bromo-2'-deoxyuridine (BrdUrd) per animal and/or at the age of 3 months to a single total-body X-ray irradiation at a dose of 1.5 Gy. In males, treatment with BrdUrd alone decreases the latency of all tumors, increases the incidence of malignant tumors and their number per rat, in comparison with control. Combined exposure to BrdUrd and X-irradiation increases total and malignant tumor yield and multiplicity over that in all other groups. More testicular Leydigomas, tumors of prostata, kidney, adrenal cortex and leukemias were seen in rats exposed to BrdUrd plus X-rays, in comparison with males treated with BrdUrd or X-irradiation alone. In females, treatment with BrdUrd alone decreases the latency of total tumors and increases their incidence and number per rat, in comparison with controls. Combined exposure to BrdUrd and X-rays did not increase total tumor incidence in comparison with only irradiated females, however, it shortened tumor latency. The incidence and multiplicity of malignant tumors, incidences of pituitary adenomas, mammary adenocarcinomas and uterine polyps were significantly increased whereas the latency of kidney tumors was decreased in females exposed to BrdUrd plus X-rays, in comparison with all other groups. These data together with other studies provide the evidence that sole perturbations of DNA induced by a nucleoside analogue, BrdUrd, contributed substantially to the tumor development and enhanced the sensitivity of target cells to carcinogenesis induced by X-irradiation as well as by chemicals or hormones.