Aspects of the regulatory function of adenosine triphosphate on the radiation sensitivity of saccharomyces cerevisiae

The possibility of influencing the radiation sensitivity by manipulation of the intra-cellular adenosine-triphosphate (ATP) concentration has been observed in diploid yeast cells. The length of the shoulder in the dose/effect curve of a respiratory deficient mutant could be decreased by pre-irradiation treatment of the cells with 2-deoxy-D-glucose (2-DG) and could be increased by incubation with glucose. Measurement of ATP concentration during liquid holding of the cells demonstrates that a minimum ATP concentration is a prerequisite for the repair of potentially lethal damage. The endogenous energy source for liquid holding reactivation is glycogen; inhibition of glycolysis with 2-DG quantitatively stops breakdown of glycogen, which causes a drastic decrease of both ATP concentration and ATP flux, so that liquid holding reactivation is no longer possible. Treatment of the mutant with glucose changes significantly its radiation sensitivity in two ways: (i) the ATP concentration increases, which leads to a longer shoulder; (ii) the ATP flux is stronger which, together with the higher ATP concentration, enables the mutant cells to carry out liquid holding reactivation. Quantitative experimental data are given. The two strains react quantitatively differently for equal concentrations of 2-DG, so that a selective radiation damaging of one of the populations is possible. Possible applications in radiation therapy are discussed. (author)