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Transplacental Exposure to Ethylnitrosourea and Its Effects on Body, Brain, and Cerebellar Development in the Rat¹

Department of Anatomy and Specialized Cancer Research Center, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033

The effect of transplacental exposure to N-ethyl-N-nitrosourea (ENU) on body, brain, and cerebellar development was studied in rats. Female Sprague-Dawley albino rats received i.p. injections (15, 60, 100, or 150 mg/kg) of ENU on the 18th day of gestation. Mothers receiving 60 mg/kg or greater had a decreased litter size and offspring with a high incidence of mortality. ENU treatment had a pronounced effect on prenatal development, and alterations in preweaning body and brain growth were also observed. Offspring subjected to injections of ENU (60, 100, and 150 mg/kg, respectively) were the most severely affected, with reductions in body weight (15, 31, and 30%, respectively), brain weight (7, 36, and 29%, respectively), and cerebral width (4, 10, and 11%, respectively) recorded at weaning (Day 21). Neonatal brain:body weight ratios showed that ENU caused greater changes in fetal neuroontogeny than in somatic development; however, ratios were similar for experimental and control pups for the remainder of the preweaning period. Cerebellar weight gain in ENU-treated pups differed from that of controls during postnatal development, but only rats treated at a dose of 60 mg/kg experienced significant cerebellar weight reduction (12%) at Day 21. Measurements of cerebellar width showed differences between control and ENU pups from birth to Day 21, and at weaning offspring treated with 15, 60, 100, and 150 mg/kg, respectively, had deficits of 6, 8, 12, and 14%, respectively. Cerebellar:brain weight ratios indicated that the brain was often more affected by ENU than was the cerebellum. These results suggest that maternal exposure to ENU retards fetal and postnatal somatic growth and affects perinatal brain and cerebellar development.

¹ Supported by Grants DT-30, PDT-27A, and PDT-27B from the American Cancer Society and by Grants 1P30 CA18450-01 and CA22815-01 awarded by the National Cancer Institute, Department of Health, Education and Welfare.

² To whom requests for reprints should be addressed.

Received 9/ 6/77. Accepted 1/30/78.