Induction of malignant tumors in Wistar and Sprague-Dawley rats by single doses of n-butyl-nitrosourea in perinatal and juvenile phases of development.
n-butyl-nitrosourea (BNU), which is highly leukemogenic in adult rats and in young mice, was applied in a single dose of 120 mg/kg body weight to pregnant Wistar rats on day 22 post conceptionem (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 days old Wistar rats as well as to 10 and 30 days old Sprague-Dawley rats. In about 50% of the progeny tumors (predominantly neurogenic) developed both after diaplacental and after direct application of the substance on day 22 p.c. After neonatal application, almost exclusively neurogenic tumors were found in greater than 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 the rats treated neonatally revealed significant differences. This shows that the 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 post  partum (p.p.) in Sprague-Dawley rats greater than 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 is observed in comparison to the animals treated on day 10. Additionally a decrease in the rate of neurogenic tumors is accompanied by an increase of tumors outside the nervous system. Aftertreatment with single doses of BNU perinatally and on day 10 p.p. only 2 rats out of 154 animals were found to have leukemia. After application of BNU to 30 days old rats, leukemia was diagnosed in 7 out of 40 animals.
D000818:Animals; D000831:Animals, Newborn; D001932:Brain Neoplasms / Q000139:chemically induced*; D005260:Female; D008431:Maternal-Fetal Exchange; D009607:Nitrosourea Compounds / Q000009:adverse effects*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats
D009607:Nitrosourea Compounds