In Search of the Optimal Experimental Model

Abstract

The increasing concern that environmental exposures may affect mammary gland differentiation and their potential for cancer risk has placed greater emphasis on the standardization of morphometric methods for the evaluation of mammary gland development in experimental animal models. Traditional morphological studies of whole mount preparations and histological sections have provided an enormous amount of information on the degree of mammary gland development and its response to diet, endogenous and exogenous hormones, and exposures to environmental chemicals, xenoestrogens, or physical agents. Their usefulness for assessing the effect of environmental exposures on mammary gland development and differentiation at specific stages of growth will depend upon optimal specimen selection and standardization of data for comparisons among laboratories. Past and present work has clearly indicated that the study of the rat mammary gland whole mount preparations under the stereomicroscope, combined with microscopic analysis, represents an important tool for evaluating risk assessment. The identification of the terminal end bud in the mammary glands of rodents and the intermediate cell (IC) as specific targets for carcinogens indicate that the adequate identification and quantification of these structures during specific windows of development would provide sufficient information for evaluating carcinogenic response. This classical model serves as a useful tool for incorporating state-of-the-art technologies that permit the microdissection of stem cells from their specific location sites for their genomic and proteomic analysis. Knowledge gained through these studies will serve for predicting the probabilities of developing cancer by detecting early genomic or epigenetic damage occurring in stem and progenitor cells.