title: Incorporation of xenobiotic carboxylic acids into lipids by cultured 3T3-L1 adipocytes.
abstract: The study was established to assess the potential for a variety of xenobiotic aromatic carboxylic acids to be incorporated into glycerolipids. The 14C-labelled xenobiotic acids were included in incubations of cultured 3T3-L1 adipocytes under defined conditions. Lipids were extracted and identified by TLC and radioscanning. Ibuprofen, 4-(2,4-dichlorophenoxy)-butanoic acid (2,4-DB), 4-(2-methyl-4-chlorophenoxy)-butanoic acid (MCPB) and 2-(2-methyl-4-chlorophenoxy)-propanoic acid (MCPP) (all 0.5 mM) were incorporated into lipid extracts at rates of 220, 227, 199 and 21 pmol microg(-1) phospholipid/h, respectively. 2,4-Dichlorophenoxyacetic acid (2,4-D), indomethacin, naproxen and fluroxypyr were incorporated at rates lower than MCPP or not at all. The incorporation of acids was first order to at least 1 mM acid (except MCPB: 300 microM). Triacylglycerol analogues were the major products with incorporation into diacylglycerol and phosphatidylcholine also observed. After digestion with pancreatic lipase, ibuprofen-containing triacylglycerol was unusual in that the main product was the monoacylglycerol analogue, suggesting that esterification had been at the sn-2 position. Incubation with cultured 3T3-L1 adipocytes is a useful and easy method to assess whether xenobiotic compounds can be incorporated into glycerolipids; of eight acids assessed, four (of which three have not previously been reported) were shown to form xenobiotic triacylglycerols.
authors.affiliation: Department of Agricultural Sciences, Imperial College London, Wye Campus, Wye, Ashford TN25 5AH, UK.
authors.forename: S
authors.initials: S
authors.lastname: Vickery
authors.forename: P F
authors.initials: PF
authors.lastname: Dodds
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D006017:Glycolipids / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: D002264:Carboxylic Acids; D006017:Glycolipids; D015262:Xenobiotics; C015903:glycerolglycolipids