Transplacental carcinogenicity of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone administered subcutaneously or intratracheally to hamsters

Abstract

Our previous studies have demonstrated that doses of 300–50 mg/kg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) injected subcutaneously into pregnant hamsters cause a 44% incidence of respiratorytract tumors in the offspring. In this study, we have extended the assay of the carcinogenic potency of NNK to doses ranging from 50 mg to 0.05 mg/kg body weight and to a second route of administration, intratracheal instillation, which is more relevant to inhalation of tobacco smoke by pregnant women. Among the offspring whose mothers had been injected subcutaneously with NNK (20–1 mg/kg), the total tumor incidence (57.2%–16.7%) decreased with decreasing dose levels. After intratracheal instillation of 50–0.05 mg/kg NNK the overall incidence varied from 28.6% to 50% but no dose response was observed. The main target organs were the adrenal glands (Phaechromocytomas) and nasal cavities (adenocarcinomas of the olfactory region). A low incidence of ductular adenomas of the pancreas was observed with low doses of NNK instilled intratracheally. These results demonstrate that NNK, at doses that are comparable to the cumulative exposure during a 9-month period in women, is a potent transplacental carcinogen in hamsters.