RESUMEN
It has been shown that chalone-containing substance obtained from the rat spleen decreased the mitotic activity of mouse thymocytes upon its intraperitoneal administration to animals. The maximum inhibition was observed 45 min after the injection. Thus, the substance examined has the property of G2 chalone.
Asunto(s)
Inhibidores de Crecimiento/fisiología , Mitosis , Linfocitos T/citología , Animales , Inhibidores de Crecimiento/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Índice Mitótico , Bazo/análisis , Factores de TiempoRESUMEN
The diminution of NAD level in mouse thymus lymphocytes precedes their death under the effect of various genotoxic agents and manifests itself by the time of the onset of chromatin degradation. At the same time, in vitro, NAD does not influence the activity of micrococcus nuclease of Ca2+,Mg2+-dependent endonuclease from human spleen. Stimulation of protein poly(ADP-ribosylation) by exogenous NAD does not change the sensitivity of chromatin to micrococcus nuclease. In contrast to hepatocytes, in the thymus, no inhibition of Ca2+,Mg2+-endonuclease, resulting from ADP-ribosylation, occurs which may be due to low activity of ADP-ribosyl transferase in thymocytes. Incubation of thymus lymphocytes with benzamide prior to irradiation does not inhibit chromatin degradation. It is suggested that the decrease in the NAD level is one of the indications of the injury to thymocytes which is not related to the induction of their death. In contrast to thymocytes, the pretreatment of Ehrlich ascites tumor cells with benzamide produces a radiosensitizing effect.
Asunto(s)
Cromatina/efectos de la radiación , NAD/metabolismo , Azúcares de Nucleósido Difosfato/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Linfocitos T/efectos de la radiación , Animales , Benzamidas/farmacología , Masculino , Ratones , Linfocitos T/efectos de los fármacosRESUMEN
A decrease in the endogenous NAD content that occurs immediately after gamma-irradiation of thymus lymphocytes is attributed to activation of poly (ADP-ribosylation) and not to changes in the activity of NAD-glycohydrolase and/or to the release of NAD from cells. The addition of benzamide 60 min before irradiation prevents the postirradiation drop of the NAD level and produces a radioprotective effect. At the same time, benzamide inhibits nuclear superhelix DNA repair and causes an average of 40 per cent decrease in the activity of DNA ligases I and II. The authors discuss the idea that the content of intracellular NAD in thymocytes is a critical factor responsible for the vitality of these cells.
Asunto(s)
NAD/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Tolerancia a Radiación , Linfocitos T/efectos de la radiación , Animales , Benzamidas/farmacología , ADN Ligasas/metabolismo , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , ADN Superhelicoidal/efectos de los fármacos , ADN Superhelicoidal/efectos de la radiación , Ratones , Linfocitos T/efectos de los fármacos , Linfocitos T/fisiologíaRESUMEN
The inhibitors of poly(ADP-ribose) polymerase did not exert a radiomodifying effect on thymocytes. The inhibitors did not also influence single-strand breaks repair in DNA of nucleoids of irradiated cells. The participation of poly(ADP-ribosylation) system in increasing the availability of thymocyte DNA damages for repair enzymes was hardly probable since benzamide in these cells did not influence the level of spontaneous genome lesions recognized by endonucleases. A possible role of protein poly(ADP-ribosylation) in thymocyte DNA repair is discussed.