Effect of diisopropanolamine upon choline uptake and phospholipid synthesis in Chinese hamster ovary cells.
Aminoalcohols differ in mammalian toxicity at least in part based upon their ability to alter the metabolism of phospholipids and to cause depletion of the essential nutrient choline in animals. This study examined the incorporation of diisopropanolamine (DIPA) into phospholipids (PLs) and effects of DIPA upon choline uptake and phospholipid synthesis in Chinese hamster ovary (CHO) cells. Results were compared to those of a related secondary alcohol amine, diethanolamine (DEA), whose systemic toxicity is closely associated with its metabolic incorporation into PLs and depletion of choline pools. DIPA caused a dose-related inhibition of (3)H-choline uptake by CHO cells that was approximately 3-4 fold less potent, based upon an IC50, than that reported for DEA. DIPA, in contrast to DEA, did not cause changes in the synthesis rates of (33)P-phosphatidylethanolamine, (33)P-phosphatidylcholine or (33)P-sphingomyelin at either non-toxic or moderately toxic concentrations. Only approximately 0.004%, of administered (14)C-DIPA was metabolically incorporated into PLs, over 30-fold less than the incorporation of (14)C-DEA under similar conditions. Overall, these data and previous pharmacokinetic and toxicity data obtained in vivo suggests that DIPA is distinct from DEA and lacks significant choline and PL metabolism related toxicity in animals.
Stott
W T
WT
Toxicology and Environmental Research and Consulting, Building 1803, The Dow Chemical Company, Midland, MI 48674, United States. wtstott@dow.com
Kleinert
K M
KM
D000818:Animals; D016466:CHO Cells; D002794:Choline / Q000493:pharmacokinetics*; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology* / Q000633:toxicity; D008082:Lipotropic Agents / Q000493:pharmacokinetics*; D010743:Phospholipids / Q000096:biosynthesis*; D011412:Propanolamines / Q000494:pharmacology* / Q000633:toxicity
D004983:Ethanolamines; D008082:Lipotropic Agents; D010743:Phospholipids; D011412:Propanolamines; C060040:diisopropanolamine; C020283:diethanolamine; D002794:Choline