Changes induced in estrogen and progesterone receptor levels by polycyclic hydrocarbons under conditions of hormonal manipulation in uterine and mammary tissues will be investigated using charcoal adsorption and sucrose gradient centrifugation. Separation of the endo-from myometrium using enzymes, followed by the separation of the glandular from stromal epithelia using discontinuous albumin gradients will be used in similar investigations. It will be determined whether DMBA is a progestin or an anti-progestin using histological changes induced in the endometrium in rabbit and the deciduoma formation in rat. Characterization of 7,12-dimethyl benz(a)anthracene (DMBA) interaction with progesterone receptors will be performed, employing in addition to the above techniques, gel filtration, polyacrylamide gel electophoresis and isoelectric focussing. It will be determined whether the translocation of 3,9-dihydroxybenz(a)anthracene (3,9-diOHBA) and DMBA, from the cytoplasm into the nuclei, and interaction with a region on the genome is due to the binding of the carcinogens to specific steroid receptors. Variations induced by 3,9-diOHBA in the synthesis of the estrogen responsive protein, "induced protein" in rat uterus will be investigated employing radiolabeled amino acid incorporation and polyacrylamide gel electrophoresis. Similarly the variations induced by DMBA in the synthesis of the progesterone induced protein, blastokinin in rabbit uterus, will be determined using gel-filtration and anti-blastokinin anti-bodies for the isolation and detection of blastokinin. These investigations offer a model to study the role of steroid hormones in carcinogenesis of the endometrium and the mammary tissue.
NIH ExPorter
NIH ExPorter