INDUCTION OF MALIGNANT-TUMORS IN WISTAR AND SPRAGUE-DAWLEY RATS BY SINGLE DOSES OF N-BUTYL-NITROSOUREA IN PERINATAL AND JUVENILE PHASES OF DEVELOPMENT

  • 1 January 1978
    • journal article
    • research article
    • Vol. 48  (1) , 9-16
Abstract
N-Butyl-nitrosourea (BNU), which is highly leukemogenic in adult rats and young mice, was applied in a single dose of 120 mg/kg body wt to pregnant Wistar rats on day 22 postconceptionem (p.c.). In another group the same dose was injected directly to fetuses of Wistar rats on day 22 p.c. after surgical delivery with subsequent feeding by nurses. The same single dose was given to 1 and 2 day old Wistar rats as well as 10 and 30 day old Spraque-Dawley rats. In about 50% of the progeny tumors (predominantly neurogenic) developed after diaplacental and direct application of the substance on day 22 p.c. After neonatal application, almost exclusively neurogenic tumors were found in > 85% of the treated juvenile animals. Comparison of survival time and tumor rates between the rats treated diaplacentally or directly on day 22 p.c. and rats treated neonatally revealed significant differences. Nervous tissue of the rat is less sensitive to BNU prenatally than in the neonatal phase of development. After application of BNU on day 10 postpartum (p.p.) in Sprague-Dawley rats > 95% of the animals developed almost exclusively neurogenic tumors with a high percentage of brain tumors. After a single dose on day 30 p.p. a significant increase in survival time and a significant decrease in the total tumor yield was observed in comparison to animals treated on day 10. A decrease in the rate of neurogenic tumors was accompanied by an increase of tumors outside the nervous system. After treatment with single doses of BNU perinatally and on day 10 p.p. only 2 of 154 rats had leukemia. After application of BNU to 30 day old rats, leukemia was diagnosed in 7 of 40 animals.

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