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Dose-related Reduction by Prenatal X-Irradiation of the Transplacental Neurocarcinogenicity of Ethylnitrosourea in Rats¹

Children's Hospital Research Foundation Institute for Developmental Research [H. K., I. O., J. W.], and Departments of Pediatrics [H. K., J. W.] and Pathology [T. I. M.], University of Cincinnati College of Medicine, Cincinnati, Ohio 45229

Pregnant Sprague-Dawley rats were X-irradiated on the 16th day of gestation with 5 to 250 rads and given i.p. injections 4 days later with 10 mg ethylnitrosourea per kg. The offspring were observed over their life span for the appearance of neurogenic tumors. The frequency of animals surviving beyond 4 weeks of age that developed tumors was inversely related to X-ray dose. About 15% developed tumors after exposure to the largest doses, 39 to 46% after the intermediate doses, and 58 to 65% after the smallest doses; 69% tumors occurred after treatment with ethylnitrosourea alone. The reductions in tumor frequency were not due to the increased mortality rate of tumor-prone animals, either before or after the onset of tumor appearance. Mean offspring weight at 4 weeks and 4 months of age was inversely related to X-ray dose but was not significantly different in those animals later developing tumors from that in animals remaining tumor free. Mean time of tumor appearance and mean number of tumors per affected animal were unrelated to tumor frequency. It does not seem that the destruction of target cells is by itself sufficient to explain the results.

¹ Supported in part by American Cancer Society Grant PDT-61.

² To whom requests for reprints should be addressed, at Children's Hospital Research Foundation, Cincinnati, Ohio 45229.

Received 2/25/80. Accepted 7/30/80.