Oxidative phosphorylation and energy status in doxorubicin-sensitive and doxorubicin-resistant Guerin carcinoma

The indices of energy status and mitochondria oxidative phosphorylation in Guerin carcinoma with different sensitivity to doxorubicin were studied. AT P, ADP and AMP contents were estimated by thin-layer chromatography. The mi tochondria oxidative phosphorylation indices were studied by the polarograp hic method with the covered combined platinum electrode. On the first stage of resistance development (after 5-8 courses of the treatment) the mitocho ndria oxygen consumption rate (in presence of succinate or glutamate) durin g phosphorylation of ADP in doxorubicin-resistant tumors was lower than in drug-sensitive tumors. On the second stage of resistance development (after 16-20 courses of the treatment) this index in drug-resistant tumors, on th e contrary, was higher than in doxonrubicin-sensitive tumors. The ATP/O rat io in mitochondria of all substrains of Guerin carcinoma was practically eq ual. The ATP level in doxorubicin-resistant tumors (stages I and II) was lo wer as compared with drug-sensitive variant. On the other hand the AMP leve l was higher in drug-resistant carcinomas (stages I and II) than in sensiti ve substrain.