EFFECTS OF SINGLE DOSES OF IRRADIATION ON THE EXPRESSION OF RESISTANCE-RELATED PROTEINS IN MURINE NIH 3T3 AND HUMAN LUNG-CARCINOMA CELLS

In this report the effects of single doses of ionizing radiation on th e mRNA expression of several proteins involved in multiple drug resist ance were analyzed. Murine NIH 3T3 cells treated with single doses of 5, 10 and 20 Gy during the time interval from 1.5 to 72 h after irradi ation were compared with their corresponding controls at the same poin ts of time. The glutathione S-transferase-pi (GST pi) level was elevat ed in cells treated with 10 or 20 Gy from 24 to 72 h after irradiation compared with the control. Topoisomerase II alpha and thymidylate syn thase were decreased in irradiated cells 24-72 h after exposure. These down-regulations were associated with cellular proliferation. determi ned by mRNA expression of the proliferation marker histone 3. Irradiat ed cells exhibited no alteration in the P-glycoprotein or glutathione peroxidase mRNA content. The finding that GST pi mRNA was overexpresse d after irradiation was validated by investigations on a human lung ca rcinoma cell line (LXF 289) on the mRNA and protein level. Thus, our r esults indicate that irradiation alters the expression of proteins inv olved in multidrug resistance and may, therefore, play a role in clini cal drug response.