Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation

摘要

The overall goal of this project was to explore the toxic effects of physical and chemical carcinogens on the immature mammary gland as compared to the effects on the young adult mammary gland using a rat model. We have: (1) completed all comparative cytotoxicity studies showing that the immature mammary gland is more sensitive to radiation and NMU but not DMBA, (2) adapted the 'Big Blue' mutagenesis assay to the mammary gland and produced data suggesting the immature gland is more susceptible to NMU mutagenesis, (3) completed radiation and chemical carcinogenesis studies, (4) adapted the comet assay to primary mammary cells and (5) identified numerous genes that are either up or down regulated in the immature mammary gland. We feel these studies will help mechanistically define the epidemiological observation in women which suggests that the immature mammary gland is more susceptible to environmental carcinogens than is the adult gland.