Dimethylamine formation in the rat from various related amine precursors.
Dimethylamine is the immediate precursor of dimethylnitrosamine, a known potent carcinogen in a wide variety of animal species. Although small amounts of dimethylamine are ingested directly, the major dietary source is believed to be via choline and related materials. Owing to quantitative recoveries following oral administration, urinary dimethylamine levels provide good overall measures of body exposure. The oral administration of equimolar amounts (1 mmol/kg body weight) of potential amine precursors to male Wistar rats produced only small increases in urinary dimethylamine after choline (+ 11%; 0.60 +/- 0.36% dose), dimethylaminopropanol (+ 32%; 1.49 +/- 0.30% dose), dimethylaminoethyl chloride (+ 110% 5.38 +/- 1.72% dose) and trimethylamine (+ 51%; 1.6 +/- 0.80% dose) input, whereas significantly larger increases were found following trimethylamine N-oxide ingestion (+ 355%; 12.93 +/- 1.13% dose; t-test, P < 0.001). These data suggest that trimethylamine N-oxide is a major dietary source of dimethylamine, by direct conversion and not by sequential reduction (to trimethylamine) and demethylation, and that in this respect it is of greater importance, on a molar basis, than choline.
Zhang
A Q
AQ
Molecular Toxicology, Division of Biomedical Sciences, Imperial College School of Medicine, London, UK.
Mitchell
S C
SC
Smith
R L
RL
D000284:Administration, Oral; D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004123:Dimethylamines / Q000652:urine*; D005021:Ethylamines / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D008744:Methylamines / Q000008:administration & dosage / Q000494:pharmacology*; D016877:Oxidants / Q000008:administration & dosage / Q000494:pharmacology*; D020005:Propanols / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D004123:Dimethylamines; D005021:Ethylamines; D008744:Methylamines; D016877:Oxidants; D020005:Propanols; C114992:dimethylaminopropanol; C114993:dimethylaminoethyl chloride; C034516:dimethylamine; C005855:trimethyloxamine; C023336:trimethylamine; D002794:Choline