Characterization of breast cancer progression in the rat.

The incidence of breast cancer is continuously increasing worldwide. This increasing trend is attributed partly to the fact that a considerable number of cases are related to environmental factors and partly to the little information available on the early changes that occur during mammary gland carcinogenesis. To characterize some of these early cellular changes, breast cancer was induced in female rats using a single intragastric dose of the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA; 80 mg/kg body weight). Mammary gland tissues of control and DMBA-treated rats were processed for routine histopathological examination and immunohistochemical analysis using an antibody specific for the proliferating cell nuclear antigen (PCNA). Microscopic examination of all mammary glands of DMBA-treated rats revealed a wide range of preneoplastic stages in addition to the well-characterized benign and malignant tumors that developed. The first stage was characterized by slightly dilated terminal ducts with accumulation of dead cells. This was designated the stage of cell death. Then, stages of hyperplasia, dysplasia, and carcinoma in situ followed. Immunohistochemical localization of PCNA in these preneoplastic lesions revealed an initial decrease followed by a gradual increase in the labeling index of PCNA. In conclusion, the DMBA-treated rats provide a useful model to dissect the early changes that occur during the multistep process of mammary gland carcinogenesis.

Retinol enhances differentiation of the gastric parietal cell lineage in developing rabbits.

In the gastric glands, parietal cells are the targets for anti-ulcer drugs because they contain the proton pump or HK-ATPase responsible for acid secretion. Little is known about factors influencing developmental expression and activity of HK-ATPase. In this study, the parietal cell lineage was investigated in rabbits at post-natal days 0 (P0) to P60 by using morphological and biochemical methods. Immunohistochemical and ultrastructural studies show that the HK-ATPase-expressing cells that appear at P0 and P3 are pre-parietal cells. However, terminally differentiated, mature parietal cells make their appearance at P7. These data correlate with the activity of HK-ATPase, measured as K(+)-dependent hydrolysis of p-nitrophenyl phosphate. Three-day-retinol treatment of P3-P30 rabbits induced an increase in the (i) production of parietal cells, (ii) intensity of the HK-ATPase immunostaining per cell, (iii) activity of HK-ATPase and (iv) amount of HK-ATPase protein measured by Western blotting. In conclusion, retinol upregulates the development of HK-ATPase in rabbits, perhaps due to precocious acceleration of the differentiation program of parietal cell lineage.