GTP influences the binding of vincristine in human tumor cytosols.
The influence of GTP on the formation and stability of [3H] vincristine (VCR)-tubulin complexes in cytosols from two human rhabdomyosarcoma xenografts which have different sensitivities to VCR has been evaluated. After removal of endogenous GTP the initial rate of [3H]VCR binding and the maximal level of bound drug were 2- to 3-fold higher in the presence of 0.1 mM GTP than in its absence. Similarly, the stability of complexes was GTP-dependent. Complex formed from Rh18 tumors, only moderately sensitive to VCR, dissociated at 37 degrees in the absence of GTP with a half-time of 67 min; complex from Rh12 tumors (exquisitely sensitive to VCR) was more stable. Neither complex dissociated in the presence of 0.1 mM GTP over 2 hr examined.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental; D014404:Tubulin / Q000378:metabolism*; D014750:Vincristine / Q000378:metabolism*
D014404:Tubulin; D014750:Vincristine; D006160:Guanosine Triphosphate