Enhanced transcription of the cytosolic ALDH gene in cyclophosphamide resistant human carcinoma cells.

Cyclophosphamide, an important cancer chemotherapeutic agent, has been shown to be effective against some types of cancer (Hilton, 1984a; Manthey and Sladek, 1989). However, both natural and acquired resistance to cyclophosphamide limits its utility in the clinic. Several investigators have observed a dramatic increase (about 200-fold) of cytosolic aldehyde dehydrogenase (ALDH, EC 1.2.1.3) activity in a cyclo-phosphamide-resistant murine leukemia cell line. It has been proposed that ALDH which can oxidize aldophosphamide, an intermediate metabolite produced from cyclophosphamide, prevents the generation of tissue toxic phosphamide mustard within cells (Manthey and Sladek, 1989; Russo et al., 1989). The drug resistance of the murine cell line with high ALDH activity can be explained by this mechanism.

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