A significant number of women who smoke are also addicted to alcohol and fail to refrain from either habit during pregnancy. Mainstream smoke of American cigarettes contains significant amounts (17-180ng/cigarette) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) but substantially larger amounts (ratio NNK/nicotine 1:17,000-1:247,000) of nicotine. NNK is a potent respiratory tract carcinogen in adult Syrian golden hamsters. During the past 2.5 years of funded support of this project we have established that: 1. NNK is a potent transplacental carcinogen in hamsters when given at high doses; 2. NNK crosses the placental barrier in hamsters and is found in significant amounts in fetal organs; 3. NNK is metabolized by alpha-carbon hydroxylation in fetal tracheas and lungs; 4.NNK causes chromosomal aberrations in fetal tracheas and lungs and induces micronucleus formation in fetal polychromatic erythrocytes. We propose to use the hamster model system to: 1. Further define the potency of NNK as transplacental carcinogen by using lower dose levels and exposure via the respiratory tract; 2. Assess the modulating effects of ethanol and nicotine and transplacental NNK carcinogenesis. All experiments will use established procedures as endpoints which have been successfully applied during the past project period. These endpoints are: studies on NNK distribution and metabolism to DNA-methylating and clastogenic intermediates in conjunction with bioassay experiments. Results from these studies could provide important experimental bases for epidemiological surveys of cancer risks associated with in utero exposure to tobacco smoke.
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