Role of Free Radicals in an Adriamycin-resistant Human Small Cell Lung Cancer Cell Line1

In two Adriamycin (Adr) resistant sublines ((•! X4-Adr, and GLQVdri) of a human small cell lung carcinoma cell line, (¿IX'4, crossresistance for radiation was found. GIXVAdr, has an acquired Adr resistance factor of 44 after culturing without Adr for 20 days and GLC4Adr2, the same subline cultured without Adr for 3 months, has a decreased but stable resistance factor of 8. One of the assumed mechanisms of Adr is that the effect is mediated through the formation of free radicals. Therefore free radical scavenging might play a role in these Adr resistant cell lines. Adr, H2O2,and X-ray induced cytotoxicity were evaluated. Glutathione (GSH) levels and activities of associated enzymes were determined as well as Adr, I l;O,, and X-ray induced DNA breaks and repair. GSH level was decreased in GLG-Adn, but restored to the normal level in GI X4-Adr;. Superoxide dismutase, catalase, glutathione-peroxidase, and glutathione 5-transferase were not elevated in the resistant sublines. Adr induced a decreased amount of DNA breaks in GIXV Adr, compared to GIX '4. For X-ray and IIX), a comparable amount of DNA damage was found. GIX>Adr, was able to repair DNA breaks induced by Adr, Xray, and II2O2 better than GLC4. In conclusion, no increased enzyme capacity for detoxification of free radicals could be detected in the cytosol of the resistant cells. The resistance against free radicals in the GLCVAdr, line may at least in part be a result of increased DNA repair.