The disposition and metabolism of N-nitrosodiethylamine in adult, infant and foetal tissues of the Syrian golden hamster.

Abstract

Low-temperature whole-body autoradiography in Syrian golden hamsters, 11 and 15 days pregnant, given N-14C-nitrosodiethylamine, indicated an ability of the non-metabolized substance to freely pass the cellular membranes of the maternal, placental and foetal tissues. Experiments in vitro with tissues of adult hamsters showed a capacity of the nasal olfactory and respiratory mucosa, the trachea, the lung, the lateral nasal gland, the liver and the kidney to degrade the N-nitrosodiethylamine. Autoradiography showed a localization of non-volatile N-14C-nitrosodiethylamine metabolites in these tissues in vivo. Since the mentioned tissues are the targets for the N-nitrosodiethylamine-induced neoplastic or preneoplastic lesions in the hamster, our results indicate that the ability of the sensitive tissues to perform the degradation of the substance is correlated to the tumour organotrophy. The main targets for the N-nitrosodiethylamine carcinogenicity - the nasal olfactory and respiratory mucosa and the trachea - were found to be very active in degrading the substance, and it was shown that cytochrome P450 is present in these tissues. Microautoradiography of the nasal mucosa showed the highest labelling over the subepithelial glands (Bowman's glands) in the olfactory region, but other areas were also labelled. In the 15 day pregnant hamster, autoradiography showed a marked in vivo localization of non-volatile metabolites in the foetal nasal and tracheo-bronchial mucosa and liver, which was not observed in the 11 day pregnant hamster. The in vivo data were shown to correlate to an in vitro capacity by the nasal mucosa, the lung and the liver of the 15 day old foetus to metabolize the substance. N-nitrosodiethylamine is a transplacental carcinogen only when administered on one of the last four days of pregnancy (day 12-15), and our results are in accord with the assumption that only at this late stage of pregnancy has the differentiation of the sensitive tissues reached a stage at which the substance can be metabolized to its ultimate carcinogen. In vitro experiments in 4, 10, and 20 day old infant hamsters showed a high capacity of the nasal mucosa, the lung and the liver to metabolize the N-nitrosodiethylamine at these early stages of life.