A new approach to the control mechanisms in tumor cells

Abstract

A new type of “perturbation” technique for the study of cellular control mechanisms is presented: when a substrate S of a particular E ( s) -enzyme is “perturbed” through a very gentle irradiation, and then tested in the corresponding enzymic reaction, dose-dependent oscillations in the activity of E ( s) -enzyme are recorded. In a series of reactions of the ▪ type or in a series of branched reactions of the ▪ type, the oscillations induced by the corresponding “perturbed” substrates in the activity of the respective enzymes were found to be non overlapping. A typical biochemical “flip-flop” is thus obtained. The pyruvate⇌lactate, glutamate⇌α-oxoglutarate and aldolase-FDPase “flip-flop” reactions realized with low level u.v.-irradiated substrates were investigated on Ehrlich-ascites tumor cells. Unexpected results were recorded. In the pyruvate⇌lactate reaction, the oscillations in the LDH activity could be induced only by u.v.-irradiated pyruvate, but not also with u.v.-irradiated lactate. The accumulation of lactic acid by tumoral tissues may be analyzed in this context. Likewise, in the glutamate⇌α-oxoglutarate reaction, the oscillations in the GDH activity could be induced only by u.v.-irradiated glutamate, but not also with u.v.-irradiated glutarate. In the aldolase-FDPase reaction, the oscillations are induced in the aldolase activity at very low-“perturbation” (i.e. irradiation) energies of fructose 1,6 diphosphate, providing a molecular model for the intense glycolytic flux of tumor tissues. The relevance of the new type of approach for the study of control mechanisms in tumor cells is discussed.