P. Kestell, Adrian P. Gledhill, M. Threadgill
Jul 15, 1986
Citations
0
Influential Citations
33
Citations
Journal
Biochemical pharmacology
Abstract
Abstract N-Methylformamide (NMF, NSC 3051) is an antineoplastic agent in mice[1,2]. In clinical trials in which the potential of NMF for the therapy of human cancers was evaluated, manifestations of liver damage were observed[3,4,5].The mouse appears to be particularly sensitive to the hepatotoxic properties of NMF[6,7] and results of mechanistic studies in mice suggest that a reactive metabolite of NMF is responsible for its hepatotoxicity[7.8]. Whereas NMF is metabolised in vitro only to a very minor extent by liver fractions or isolated mouse hepatocytes, it undergoes extensive metabolism in vivo in rodents[9]. Carbon dioxide, methylamine and N-hydroxymethylformamide have been identified as major metabolites of NMF[10].In that study, a further metabolite was detected but not characterised. We now report the identification of a new urinary metabolite of NMF and suggest that its precursor(s) may well be responsible for the hepatotoxicity and/or the antitumour activity of NMF.