RESUMO
Biologically active small-molecular-weight compounds are actively transported into the cell nucleus by a specific receptor. This has been widely demonstrated for retinoids, polycyclic hydrocarbons (such as steroids), and dioxin. Thus, it is reasonable to assume that genotoxically active polycyclic hydrocarbons, and possibly all genotoxically active small-molecular-weight substances, exert their transformational effect in the cell nucleus via a specific receptor. I propose that the receptor is activated only at the end of the G(1) phase of the cell cycle and that the carcinogen receptor complex interferes directly with DNA synthesis, leading to mutations. This hypothesis may account for various characteristics of malignant growth, such as the organ specificity of carcinogens and the relationship between cell proliferation and malignant transformation. If so, it could form the basis for establishing a radioreceptor assay for carcinogens.
Assuntos
Carcinógenos/metabolismo , Carcinógenos/farmacologia , Modelos Biológicos , Receptores Citoplasmáticos e Nucleares/metabolismo , Transporte Ativo do Núcleo Celular , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Fase G1 , Mutagênese/efeitos dos fármacos , Mutagênicos/metabolismo , Mutagênicos/farmacologia , Especificidade de Órgãos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismoAssuntos
Receptores de Superfície Celular , Aldosterona , Androgênios , Animais , Mama , Estrogênios , Feminino , Glucocorticoides , Humanos , Túbulos Renais , Fígado , Pulmão , Sistema Linfático , Oviductos , Progesterona , Esteroides , ÚteroAssuntos
Peptídeos , Receptores de Superfície Celular , Tecido Adiposo , Glândulas Suprarrenais , Hormônio Adrenocorticotrópico , Membrana Celular , Feminino , Glucagon , Gonadotropinas , Humanos , Insulina , Fígado , Masculino , Monócitos , Mutação , Neoplasias , Ovário , Testículo , TimoRESUMO
The specific binding of 125I-labelled human chorionic gonadotrophin (HCG) by rat testicular homogenate as compared with isolated Leydig cells differs with respect to total binding capacity but not to the dissociation constant (Kd) as revealed by Scatchard analysis. The maximal binding capacity for [125I]HCG of crude testicular homogenate was 95 ng/g rat testis. Hypophysectomy causes a decline in binding capacity within the first three days but on the 20th and 30th day after hypophysectomy the relative binding capacity no longer differs from that of controls. Binding capacity is enhanced in cryptorchid testes relative to normal, and increases during sexual maturation to a peak shortly before puberty.