RESUMO
A 3-h exposure to NO donors (spermine-NO, DETA-NO, or SNAP), or to NOS II-expressing cells (activated macrophages or EMT6 cells) reversibly inhibited DNA synthesis in K562 tumor cells. In GSH-depleted K562 cells, cytostasis remained reversible when induced by DETA-NO or NOS II activity, but became irreversible after exposure to spermine-NO or SNAP. Only SNAP and spermine-NO efficiently inhibited GAPDH, an enzyme with a critical thiol, in GSH-depleted cells. Thus, the irreversible cytostasis induced in GSH-depleted cells by spermine-NO or SNAP can be tentatively attributed to S-nitrosating or oxidizing species derived from NO. However, these species did not contribute significantly to the early antiproliferative effects of macrophages. Ribonucleotide reductase, a key enzyme in DNA synthesis. has been shown to be inhibited by NO. Supplementation of the medium with deoxyribonucleosides to bypass RNR inhibition restored DNA synthesis in target cells exposed to DETA-NO and NO-producing cells, but was inefficient for GSH-depleted cells previously submitted to spermine-NO or SNAP. These cells also exhibited a persistent depletion of the dATP pool. In conclusion, GSH depletion reveals striking qualitative differences in the nature of the toxic effectors released by various NO sources, questioning the significance of S-nitrosating or oxidizing nitrogen oxides in NOS II-dependent cytostasis.
Assuntos
Antineoplásicos/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/biossíntese , Animais , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA de Neoplasias/biossíntese , Nucleotídeos de Desoxiadenina/metabolismo , Desoxirribonucleotídeos/metabolismo , Radicais Livres/metabolismo , Glutationa/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Humanos , Macrófagos/metabolismo , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Óxidos de Nitrogênio , Penicilamina/análogos & derivados , Penicilamina/farmacologia , Ribonucleotídeo Redutases/metabolismo , Espermina/análogos & derivados , Espermina/farmacologia , Triazenos/farmacologia , Células Tumorais CultivadasRESUMO
The clinical trial involved 31 cases, 10 in stomatology. Acupuncture may produce analgesia after simple premedication. Of 21 abdominal operations, in 5 completion of effect using local infiltration of a few millilitres of lignocaine or intravenous pentazocine was required. In 7, general anaesthesia was required to complete the operation. All patients not receiving supplementary general anaesthesia were able to eat normally as soon as they were back in bed, passed flactus the same day and had a bowel movement the next day. Ten stomatological operations may be considered to be successful. Further pursual of these trials is justified.