Murine dorsolateral prostate has been shown to undergo estrogen and chemical carcinogen-induced neoplastic transformation. We propose to use organ cultures of this tissue to test the concept that sex hormones promote the action of chemical carcinogen by modulating prostatic basal-cell proliferation and epithelial differentiation. After explant pre-treatment with a direct-acting and indirect-acting carcinogen (methyl-N'-Nitro-N-nitrosoguanidine and 7,12-dimethylbenz[a]anthracene), sex hormone effects in prostate culture will be compared with those of known carcinogenesis promoters. Seminal vesicles which rarely undergo spontaneous neoplastic transformation will serve as tissue control. Epithelial-cell proliferation as measured by mitotic indices and morphological parameters of cellular differentiation will be correlated with changes in ornithine decarboxylase activity and patterns of C19-radiosteroid disposition. The latter will focus on 5Alpha-dihyrotestosterone formation, high-affinity binding and explant egress by means of the 3Beta-hydroxysteroid pathway. We intend to continue studies on the disposition of natural radioisotope-labeled androgens in organ cultures of murine and canine prostate and human prostate and human prostate adenoma and adenocarcinoma. Special emphasis will be on interactive contributions of the testicular and adrenal Lamda5-3Beta-hydroxyC19-steroids to testosterone/5Alpha-dihydrotestosterone disposition. For evaluation of carcinogen-sex hormone action on the explants, we shall examine morphological changes with light and electron microscopy, determine changes in proliferation rate (mitotic indices) by the colcemid metaphase arrest technique, and obtain C19-radiosteroid disposition patterns by previously published chromatographic and receptor assay procedures. This work should provide insight into factors that may contribute to proliferative diseases of the prostate.
NIH ExPorter
NIH ExPorter