DIMETHYLAMINE FORMATION IN THE RAT FROM VARIOUS RELATED AMINE PRECURSORS

Dimethylamine is the immediate precursor of dimethylnitrosamine, a kno wn potent carcinogen in a wide variety of animal species. Although sma ll amounts of dimethylamine are ingested directly, the major dietary s ource is believed to be via choline and related materials. Owing to qu antitative recoveries following oral administration, urinary dimethyla mine levels provide good-overall measures of body exposure. The oral a dministration of equimolar amounts (1 mmol/kg body weight) of potentia l amine precursors to male Wistar rats produced only small increases i n urinary dimethylamine after choline (+11%; 0.60 +/- 0.36% dose), dim ethylaminopropanol (+ 32%, 1.49 +/- 0.30% dose), dimethylaminoethyl ch loride (+110% 5.38 +/- 1.72% dose) and trimethylamine (+51%, 1.6 +/- 0 .80% dose) input, whereas significantly larger increases were found fo llowing 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 th at in this respect it is of greater importance, on a molar basis, than choline. (C) 1998 Elsevier Science Ltd. All rights reserved.