Comparison of the effects of N-nitrosodimethylamine on pregnant and nonpregnant Holtzman rats

Abstract

Single oral doses of N-nitrosodimethylamine or olive oil were given to nonpregnant and pregnant female Holtzman rats on different days of pregnancy (days 7–18, where day 0 was considered to be the sperm positive day). Serological and histopathological studies were performed on animals killed 2 days after treatment. In comparison with the values obtained in nonpregnant controls, the following parameters in pregnant controls were significantly increased: relative liver weights (days 9–20), liver ascorbic acid concentrations (day 12), blood urea nitrogen (days 16–20), serum triglyceride (days 14–20), serum inorganic phosphorus (days 12–18), and serum glutamic-pyruvic transaminase (days 14–20). The following parameters were decreased in pregnant rats compared with nonpregnant controls: relative organ weights (kidneys, adrenals and thyroids), serum glucose (days 12–20), total serum protein (days 9 and 16–20), and serum alkaline phosphatase (day 20). The serum cholesterol levels in pregnant rats were significantly decreased on days 9–15 of pregnancy and significantly increased on day 20. The numbers of mitotic cells in the livers of pregnant rats were greatly increased compared with nonpregnant rats on all days of pregnancy, while the adrenal cortex contained a significantly higher number of mitotic cells only on days 16 and 18. Compared with control values, NDMA given orally (15 or 20 mg/kg body weight) increased the following in both pregnant and nonpregnant rats: numbers of mitotic cells in the liver and adrenal cortex, relative adrenal weights, serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase. NDMA treatment decreased liver ascorbic acid and total serum protein in both pregnant and nonpregnant rats. In nonpregnant rats NDMA also increased relative liver weights (not significant) and serum alkaline phosphatase levels. NDMA increased serum α-hydroxybutyric dehydrogenase in pregnant rats on day 20 and decreased foetal weights (in rats treated on days 13 and 18). NDMA treatment was not lethal to nonpregnant rats or to pregnant rats up to day 16 of pregnancy, but single oral doses of 15 and 20 mg NDMA/kg killed 9.4 and 35.3%, respectively, of rats treated on day 18 of pregnancy. In general, the acute toxic effect of NDMA, as measured by changes in the above parameters, was greater in pregnant than in nonpregnant rats, especially near the end of pregnancy.