RESUMO
The effects of the beta-isomer of hexachlorocyclohexane (beta-HCH) on the induction of the cytosolic progesterone receptor (PgRc), on the redistribution of the estrogen receptor (ER), and its affinity for ER were investigated in the estrogen-sensitive human mammary tumor cell line MCF-7. The effects of beta-HCH were compared to those of estradiol-17 beta (E2) and 2,4,6-trichlorophenol (TCP), a major urinary metabolite of beta-HCH in rats. beta-HCH in concentrations higher than 1 microM caused induction of PgRc whereas TCP was essentially without effect up to a cytotoxic concentration of 100 microM. Furthermore, beta-HCH (10 microM) caused redistribution of ER, i.e., decrease of cytosolic ER concentration and increase of nuclear ER concentration, in a way similar to E2. In contrast to this, beta-HCH up to a molar excess of 6 X 10(4) (concentration 30 microM) caused no significant displacement of [3H]E2 from ER indicating that beta-HCH has no substantial affinity for ER. It is concluded that beta-HCH has estrogenic properties which are at variance with the failure to demonstrate binding of beta-HCH to ER.
Assuntos
Neoplasias da Mama/metabolismo , Hexaclorocicloexano/farmacologia , Receptores de Estrogênio/metabolismo , Animais , Biotransformação/efeitos dos fármacos , Neoplasias da Mama/análise , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Clorofenóis/farmacologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Feminino , Humanos , Ratos , Receptores de Progesterona/efeitos dos fármacos , Receptores de Progesterona/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The total uptake and incorporation into DNA of 3H-thymidine in MCF-7 cells is stimulated by estradiol after an incubation period of 24 h. Prolonged incubations show a decreased rate of both uptake and incorporation of 3H-thymidine, but the labeling index remains elevated up to 48 h. It appears that this is the only exception to the observed good relationship between labeling index and total uptake of 3H-thymidine. This correlation may be of use in comparing autoradiographic and biochemical data on DNA synthesis in the case of culturing both primary mammary tumors and mammary cancer cell lines.
Assuntos
Neoplasias da Mama/metabolismo , Estradiol/farmacologia , Timidina/metabolismo , Autorradiografia , Divisão Celular , Células Cultivadas , DNA de Neoplasias/biossíntese , Humanos , Cinética , Estatística como Assunto , TrítioRESUMO
The levels of cyclic AMP and cyclic GMP during the second cleavage cycle of eggs of Mactra solidissima have been measured. Cyclic GMP levels vary reciprocally with cyclic AMP levels, the cyclic GMP level increasing up to 4 to 5-fold and the cyclic AMP level falling to 50 percent at the onset of mitosis.
