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Carcinogen-binding proteins in the rat ventral prostate: specific and nonspecific high-affinity binding sites for benzo(a)pyrene, 3-methylcholanthrene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1986

P Söderkvist, and L Poellinger, and J A Gustafsson

The polychlorinated dibenzodioxin [3H]-2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and the carcinogens [3H]benzo(a)pyrene and [3H]-3-methylcholanthrene bound to saturable binding sites in cytosol from the rat ventral prostate. Analysis of equilibrium binding parameters in diluted cytosol preparations indicated an apparent Kd of approximately 2 nM and a binding capacity of approximately 1 nmol/mg cytosolic protein, corresponding to approximately 5% of the total protein content. However, gel permeation chromatography analysis as well as velocity sedimentation analysis on sucrose gradients of [3H]TCDD-labeled rat prostatic cytosol indicated binding of [3H]TCDD to two discrete species. These analyses indicated a sedimentation coefficient of 3.6-3.8S, a Stokes radius of 25-28 A, and a calculated relative molecular weight of 42,000-45,000 for the most abundant binding species. The other binding species sedimented at 4-5S under high ionic strength conditions and at 8-10S under low ionic strength conditions and had a Stokes radius of approximately 60 A, a relative molecular weight of approximately 100,000 and an estimated concentration of 5-20 fmol/mg cytosolic protein. Binding of [3H]TCDD to this species was displaceable by a 200-fold M excess of 2,3,7,8-tetrachlorodibenzofuran. Therefore, this species was tentatively identified as the TCDD receptor. The properties of the high-capacity binder of [3H]TCDD were found to be similar to the characteristics of a protein previously purified from the rat ventral prostate, prostatic secretory protein, which binds androgens as well as estramustine, a nitrogen mustard derivative of estradiol. The binding of estramustine to diluted prostatic cytosol was shown to be competitively inhibited by 2,3,7,8-tetrachlorodibenzofuran. Moreover, purified prostatic secretory protein bound [3H]TCDD, [3H]benzo(a)pyrene, as well as [3H]-3-methylcholanthrene. It is suggested that binding to this protein is responsible for the high-binding capacity of carcinogens in cytosol from the rat ventral prostate.

UI MeSH Term Description Entries
D008297 Male Males
D008748 Methylcholanthrene A carcinogen that is often used in experimental cancer studies. 20-Methylcholanthrene,3-Methylcholanthrene,20 Methylcholanthrene,3 Methylcholanthrene
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011987 Receptors, Steroid Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes. Corticosteroid Receptors,Receptors, Corticosteroid,Steroid Receptors,Corticosteroid Receptor,Receptors, Steroids,Steroid Receptor,Receptor, Corticosteroid,Receptor, Steroid,Steroids Receptors
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D004147 Dioxins A family of compounds that contain the 1,4-dioxin structure. Many specific dioxin derivatives are listed as CARCINOGENS; TERATOGENS; or MUTAGENS. Dioxin
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001564 Benzo(a)pyrene A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. 3,4-Benzopyrene,3,4-Benzpyrene,3,4 Benzopyrene,3,4 Benzpyrene

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