This study will investigate the mechanism(s) whereby two environmental factors, diet and chemical carcinogens, interact at the level of the mammary gland to result in the development of mammary adenocarcinomas. Their influence on the structural and functional development of the mammary gland will be determined to ascertain whether the developmental state of either of these characteristics at the time of carcinogen exposure is a determinant in tumorigenesis. Purified diets containing high levels of polyunsaturated fat, saturated fat, or low in the fat content will be used. These diets will be supplemented with either propyl gallate or butylated hydroxytoluene (inhibitors of mammary carcinogenesis) to determine their influence on mammary gland development, both structurally and functionally. Female rats placed on these diets at weaning will be exposed to the carcinogen 7,12-dimethylbenz(Alpha)anthracene (DMBA) at critical time points, and the induction of mammary adenocarcinomas and tumor incidences monitored. Comparable sets of animals with respect to age and diet, will be used to investigate the developmental (functional) and morphological state of the gland at the time of carcinogen exposure. This information will be correlated with subsequent tumor incidences. The relationship between the stage of development of the gland in the different dietary states will be correlated with DNA labeling indices and the cellular distribution of DMBA in mammary parenchymal and fat cells by autoradiographic techniques. Fatty acid analyses will be done on mammary glands under the various dietary conditions. As a further determination of mammary gland functionality in the different dietary states, metabolism of DMBA by mammary gland microsomes will be investigated. DMBA product profiles will be compared between animals which have been fed the various diets for different periods of time. As a correlary, aryl hydrocarbon hydrolase and epoxide hydrase will be determined with respect to the age and dietary status of the animals.
NIH ExPorter
NIH ExPorter