title: Effects of the new nitrosourea derivative, fotemustine, on the glutathione reductase activity in rat tissues in vivo and in isolated rat hepatocytes.
abstract: Fotemustine, a new clinically active nitrosourea, is demonstrated herein to be a poor inhibitor of glutathione reductase activity from rat liver, lung and kidney cytosols. In order to show that an intracellular step of activation does not lead to a toxic intermediary metabolite, rat hepatocytes were incubated with fotemustine. Their glutathione-related pathways were checked and shown not to be altered, while under similar experimental conditions BCNU was shown to be dramatically harmful. Furthermore, association of fotemustine with a H2O2 production leading drug, diquat, was shown to be inefficient--while BCNU is efficient--in potentiating the diquat toxicity. Considering the role of glutathione level in the detoxification of mutagens and carcinogens, the advantage of fotemustine over BCNU in therapeutic use seems substantiated.
authors: Division de Pathologies Cancéreuses et Immunes, Institut de Recherches Servier, Suresnes, France.
authors: J A
authors: JA
authors: Boutin
authors: K
authors: K
authors: Norbeck
authors: P
authors: P
authors: Moldeus
authors: A
authors: A
authors: Genton
authors: M
authors: M
authors: Paraire
authors: J P
authors: JP
authors: Bizzari
authors: G
authors: G
authors: Lavielle
authors: C A
authors: CA
authors: Cudennec
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002469:Cell Separation; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology; D008297:Male; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D005980:Glutathione Reductase; C054368:fotemustine