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 radiationon the mRNA expression of several proteins involved in multipledrug resistance were analyzed. Murine NIH 3T3 cells treatedwith single doses of 5, 10 and 20 Gy during the time intervalfrom 1.5 to 72 h after irradiation were compared with theircorresponding controls at the same points of time. The glutathioneS-transferase- (GST) level was elevated in cells treated with10 or 20 Gy from 24 to 72 h after irradiation compared withthe control. Topoisomerase II and thymidylate synthase weredecreased in irradiated cells 24–72 h after exposure.These down-regulations were associated with cellular proliferation,determined by mRNA expression of the proliferation marker histone3. Irradiated cells exhibited no alteration in the P-glycoproteinor glutathione peroxidase mRNA content. The finding that GSTmRNA was overexpressed after irradiation was validated by investigationson a human lung carcinoma cell line (LXF 289) on the mRNA andprotein level. Thus, our results indicate that irradiation altersthe expression of proteins involved in multidrug resistanceand may, therefore, play a role in clinical drug response.