RESUMEN
The jack bean lectin, concanavalin A (Con A), was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-Con A. The immunoreactivity of PEG-Con A towards anti-Con A antibodies was reduced by increasing the degree of modification of amino groups in the Con A molecule. PEG-Con A had a complete reduction of the immunogenicity in mice and prolonged the clearance-time in blood. Although the mitogenic activity of Con A towards murine spleen cells was reduced by the conjugation with activated PEG2, the administration of PEG-Con A to mice enhanced the anti-tumor cytotoxicity of peripheral lymphocytes against melanoma B16 cells.
Asunto(s)
Concanavalina A/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Solventes/uso terapéutico , Linfocitos T Citotóxicos/efectos de los fármacos , Animales , Anticuerpos Antineoplásicos/análisis , Concanavalina A/inmunología , Concanavalina A/farmacocinética , Combinación de Medicamentos , Femenino , Hemaglutinación/efectos de los fármacos , Inmunoglobulina G/inmunología , Melanoma Experimental/sangre , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mitosis/efectos de los fármacos , Polietilenglicoles/farmacocinética , Solventes/farmacocinética , Bazo/patología , Linfocitos T Citotóxicos/patología , Células Tumorales Cultivadas/efectos de los fármacosAsunto(s)
Apoptosis/fisiología , Leucemia L1210/patología , Leucemia L5178/patología , Valina/fisiología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3 , Caspasas/metabolismo , Medios de Cultivo , Fragmentación del ADN , Isoleucina/efectos de los fármacos , Isoleucina/fisiología , Cinética , Leucemia L1210/enzimología , Leucemia L5178/enzimología , Ratones , Células Tumorales Cultivadas , Valina/farmacologíaRESUMEN
Apoptotic cell death of murine leukemia cells induced by E. coli L-asparaginase was studied. Deprivation of L-asparagine from the culture of L5178Y cells by L-asparaginase caused the fragmentation of chromosomal DNA of the leukemia cells within 24 h. Prior to the degradation of DNA, cell cycles of L5178Y cells were found to be arrested in G1 phase, and evidence of the DNA strand breaks was initially observed in G1 phase cells as early as 8 h after the asparaginase treatment. Therefore, apoptosis of leukemia cells induced by L-asparaginase is an event that is associated with the cell cycle arrest in G1 phase.