RESUMO
Dimethyl disulfide markedly increased the cytotoxicity of selenocystamine by 2 orders of magnitude, from 40 microM to 0.5 microM for 50% inhibition of growth in 45 hr. When mice were injected ip with 22 microMole/Kg of selenocystamine on Day 0, all were dead on Day 4. If dimethyl disulfide (500 microMole/Kg) was either mixed with the selenocystamine or injected immediately prior to it, the mice survived treatment for at least 21 days afterwards, suggesting that methylthio-capping of selenocysteamine reduced host toxicity. Such combined treatment may be of value in chemotherapy.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cistamina/análogos & derivados , Dissulfetos/farmacologia , Leucemia L1210/patologia , Compostos Organosselênicos , Selênio/toxicidade , Animais , Cistamina/metabolismo , Cistamina/toxicidade , Dissulfetos/metabolismo , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Técnicas In Vitro , Leucemia L1210/metabolismo , Camundongos , Selênio/metabolismoRESUMO
Selenocystine inhibited the growth in culture of murine L1210 leukemia cells to a greater extent when the cells were supplemented with a high concentration of cystine for optimal growth. Cells which grew suboptimally in a limiting cystine concentration were inhibited to a lesser extent. In this case, the time of onset of selenocystine inhibition coincided with the time of termination of growth at the lower cystine concentration. These observations are contrary to expectation for action of an antimetabolite, and it is concluded that selenocystine cannot be considered a cystine antagonist.
Assuntos
Antimetabólitos/farmacologia , Cistina/análogos & derivados , Cistina/antagonistas & inibidores , Leucemia L1210/metabolismo , Compostos Organosselênicos , Selênio/farmacologia , Animais , Células Cultivadas , Cistina/farmacologia , Leucemia L1210/patologia , CamundongosRESUMO
Metal-binding chelators may interact with biological systems by either of two mechanisms: they may combine with an essential metal, which can be either freely dissociated or part of an enzyme prosthetic group, or they may react with a metal ion to form a biologically reactive metal-chelate complex. As trace metals are always present as contaminants in serum-supplemented culture media used to study chelating agents, it is frequently difficult to distinguish between the two possibilities. Here we describe the use of a nontoxic, copper-specific chelating agent, bathocuproine sulphonate (Fig. 1) which, by combining with available endogenous copper in a tissue culture preparation, abolished the toxicity of three structurally unrelated chelating agents. These three agents may therefore be considered to be biologically active by the second mechanism.