Transplacental mutagenesis of products formed in the stomach of golden hamsters given sodium nitrite and morpholine

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Abstract
Hamster embryos were exposed in utero to the action of sodium nitrite (NaNO2) and morpholine (Mo) administered simultaneously by stomach tube to the mothers on the 11th or 12th day of pregnancy. Embryo cells were examined for chromosomal aberrations, micronuclear formation, morphological or malignant transformation and drug resistance mutations. For detection of induced mutations, the embryo cells were cultured in normal medium for 72 h and then transferred to medium containing 10 or 20 μg/ml of 8‐azaguanine (8AG) or 1 mM ouabain (Oua). The number of 8AG‐, Oua‐resistant colonies was markedly increased after administration of NaNO2 and Mo. The embryonic fibroblasts also showed a markedly increased frequency of micronucleation and a slight increase in chromosome aberrations. This treatment also caused morphological or malignant transformation of fetal cells. After cultivation in vitro, cells from some transformed colonies produced tumors when inoculated into the cheek pouch of young golden hamsters. Orally administered N‐nitroso‐morpholine (N‐Mo), as a positive control, had the same transplacental biological actions on embryonic fibroblasts. However, transplacentally Mo alone was ineffective. A single administration of 500 mg/kg NaNO2 had only slight biological effects. N‐Mo was produced in the stomachs of animals treated simultaneously with NaNO2 and Mo. A small amount of a nitrosamine, N‐nitrosodimethylamine (DMN), was detected in the stomach after a single dose of NaNO2.