Modification of the radiation induced damage by 2-deoxy-D-glucose in organ cultures of human cerebral gliomas.

Effects of a glucose antimetabolite, 2-deoxy-D-glucose (2-DG), on the gamma ray induced radiation damage have been studied in organ cultures of human cerebral gliomas. Percentage of cells with micronuclei (M-fraction) was used to assay the radiation damage. Experimental data indicate the following results. Untreated cerebral gliomas show considerable spatial heterogeneity in M-fraction; In spite of this heterogeneity, increases in M-fraction induced by gamma rays can be clearly observed, if multiple and randomly selected explants are analyzed for each group; The radiation induced M-fraction in different gliomas varies over a wide range; Presence of 2-DG (5 mM) for 4 h after irradiation leads to an increase in the radiation induced M-fraction in the majority of tumors, while in a smaller number (congruent to 25%) a decrease is observed under similar conditions. These results can be explained on the basis of a model postulating differential effects of 2-DG on the energy linked modulations of the processes of repair and fixation of DNA damage, which competitively influence the formation of micronuclei.