DETOXIFICATION ABILITY AND TOXICITY OF QUINONES IN MOUSE AND HUMAN TUMOR-CELL LINES USED FOR ANTICANCER DRUG SCREENING

The in vitro testing of antitumor drugs involves the use of mouse and human tumor cells. In particular, there is interest in developing agen ts active against human solid tumors. We examined several biochemical parameters that may contribute to the differential sensitivity of the cell lines used in our laboratory to the toxic effects of antitumor co mpounds. The tumor cell lines examined were of mouse (colon 38, L1210 leukemia, and C1498 leukemia) and human origin (GEM leukemia, CX1 colo n, H116 colon, HCT8 colon and H125 lung). Quinone reductase activity w as markedly different between leukemia and solid-tumor cell lines of e ither mouse or human origin, with increased activity being observed in the solid-tumor cell lines relative to the leukemia lines. GSH transf erase activity also was generally increased in solid-tumor relative to leukemia cell lines. Superoxide dismutase activity and thiol levels w ere similar in leukemia and solid-tumor cell lines, except that thiol levels were very low in colon 38. Mouse cell lines from in vitro passa ge had somewhat higher activity of superoxide dismutase and thiol leve ls than did cells maintained in vivo, indicating relatively increased antioxidant defenses. The toxicity of 2,3-dimethoxy-1,4-naphthoquinone , a model quinone that exerts its toxic effects via production of reac tive oxygen species, was significantly lower in mouse lines maintained in vitro than in those tested in vivo, whereas the toxicity of anothe r quinone, menadione, was just slightly lower. Quinone reductase activ ity, GSH transferase activity, and thiol levels were significantly hig her in the human lines than in the mouse lines. Accordingly, the toxic ity of both quinones tended to be lower in the human lines than in the mouse lines.