Activation of methanol by hepatic postmitochondrial supernatant: formation of a condensation product with 2,4-diaminotoluene.
2,4-Diaminotoluene, an aromatic amine hepatocarcinogen in rats and mice, reacts extensively with formaldehyde produced by the oxidation of methanol to form a single reaction product. Using 1H and 13C NMR and high-resolution mass spectroscopy, this product was shown to be bis(2,4-diamino-5-tolyl)methane. This reaction product is shown to occur under conditions whereby methanol is metabolized to formaldehyde by rat hepatic postmitochondrial supernatant. These results demonstrate a novel reaction of aromatic amines and formaldehyde in biological samples and indicate that methanol as a solvent may become activated in vitro and produce complex interactions with solutes.
Cunningham
M L
ML
Experimental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Matthews
H B
HB
Burka
L T
LT
D000818:Animals; D001711:Biotransformation; D002457:Cell Extracts; D002851:Chromatography, High Pressure Liquid; D005557:Formaldehyde / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D000432:Methanol / Q000493:pharmacokinetics*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010655:Phenylenediamines / Q000378:metabolism*; D051381:Rats
D002457:Cell Extracts; D010655:Phenylenediamines; D005557:Formaldehyde; C010914:2,4-diaminotoluene; D000432:Methanol