INFLUENCE OF pH AND GLUCOSE ADMINISTRATION ON THE PHOTOTOXICITY OF CHLORIN-Е6 TOWARDS EHRLICH CARCINOMA CELLS
I.N. Shevchuk, L.V. Chekulayeva, V.A. Chekulayev
Institute of Chemistry of Tallinn Technical University, Akadeemia tee 15, 12618 Tallinn, Estonia
Abstract. As known the pH value in malignant tumors is lower that of normal tissues and can be decreased selectively by glucose administration. The aim of the study was, therefore, to evaluate the effect of pH and hyperglycaemia on the antitumor efficiency of photodynamic therapy (PDT) with chlorin-e6 trimethyl ester (E6). For in vitro experiments, Ehrlich ascites carcinoma (EAC) cells were pre-incubated with E6 in a serum-free medium at pH 7.2 or 6.2 and were then irradiated with red light at 665 nm. It was found that their photosensitivity increased with decreasing pH value, although the cellular uptake of the sensitizer was lower by nearly 25%. In vivo experiments were performed on mice bearing EAC cells grafted subcutaneously. An apparent delay in the tumor growth was obtained by the combination of E6-PDT with a single injection of glucose (2 g/kg body weight). This administration of glucose (2 h before the PDT) caused a substantial decrease in the tumor pH from an initial value of ~ 7.2 to ~ 6.3, as measured by a needle pH electrode. Studies suggest that at low pH values the impairment of mitochondrial function as well as the inhibition of E6 photobleaching in the cells are probably the main factors as to the revealed effect of pH on the antitumor efficiency of PDT with the sensitizer.
