Chemical oxidation and metabolism of N-methyl-N-formylhydrazine. Evidence for diazenium and radical intermediates.
N-Methyl N-formlhydrazine (1), a component of the mushroom Gyromitra esculenta, is a carcinogen. Its mode of action, however, is poorly understood. To determine the intermediates that may form during the metabolism of 1, we examined its oxidative chemistry, identified the products and inferred the intermediates on the basis of these products. The incubation of 1 with rat liver microsomes was also studied and the metabolites determined and quantified. Both the chemical and the microsome-mediated oxidation of 1 yielded formaldehyde and acetaldehyde. The formation of acetaldehyde requires (i) the oxidation of 1 to a diazenium ion (I) or diazene (II) and (ii) fragmentation of I/II to formyl and methyl radicals. It is suggested that these radical intermediates may be important in understanding and elucidating carcinogenesis by 1.
Gannett
P M
PM
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68105-1065.
Garrett
C
C
Lawson
T
T
Toth
B
B
D000079:Acetaldehyde / Q000378:metabolism; D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005557:Formaldehyde / Q000378:metabolism; D005609:Free Radicals; D007094:Imides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009002:Monomethylhydrazine / Q000031:analogs & derivatives* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D005609:Free Radicals; D007094:Imides; D005557:Formaldehyde; C016577:N-methyl-N-formylhydrazine; D000079:Acetaldehyde; C038867:diazene; D009002:Monomethylhydrazine