THE ANTITUMOR-ACTIVITY OF ALKYLATING-AGENTS IS NOT CORRELATED WITH THE LEVELS OF GLUTATHIONE, GLUTATHIONE TRANSFERASE AND O-6-ALKYLGUANINE-DNA-ALKYLTRANSFERASE OF HUMAN TUMOR XENOGRAFTS

Twenty-three human xenografts, including five colon, five gastric, nin e lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC ), cyclophosphamide (CTX) and cisplatin (DDP). In 12 cases, at least o ne of the drugs produced complete or partial remission, in 2, a minor regression was observed and in the other 9, treatment was ineffective. The level of sensitivity to each drug, using a score from 1 to 5, was correlated to three biochemical parameters reported to be involved in resistance to alkylating agents: glutathione (GSH), glutathione trans ferase (GST) and O-6-alkylguanine-DNA-alkyltransferase (AGT). A wide v ariability was found in these parameters in the xenografts investigate d. No correlation was found between any of the three parameters and se nsitivity to the drugs used or between sensitivity to one drug and to any of the other drugs tested. These results illustrate the complexity of the question of resistance to alkylating agents and indicate that, at least in xenografts, the biochemical parameters examined are not p redictive of response to alkylating agents. (C) 1998 Elsevier Science Ltd. All rights reserved.