CONJUGATED LINOLEIC-ACID REDUCES ARACHIDONIC-ACID CONTENT AND PGE(2) SYNTHESIS IN MURINE KERATINOCYTES

Dietary conjugated linoleic acid (CLA) is associated with decreased 12 -O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in m ouse skin. In addition, CLA decreases TPA-induced prostaglandin E synt hesis and ornithine decarboxylase activity in cultured keratinocytes c ompared with linoleic acid (LA) and arachidonic acid (AA). When LA or CLA was added to keratinocyte cell cultures, the amounts of each of th ese cellular fatty acids increased significantly in a dose-dependent m anner. Furthermore, LA treatment was associated with increased cellula r AA while the AA content of keratinocytes was reduced when cultures w ere treated with CLA. Moreover, CLA (16 mu g/ml) was more potent than LA at decreasing the level of C-14-AA incorporated into cellular phosp hatidylcholine. In order to determine the effect of CLA on arachidonat e-derived PGE(2), the release of C-14-AA and C-14-PGE(2) synthesis was measured in cultures pre-treated with LA/C-14-AA or CLA/C-14-AA for 1 2 h. The amount of C-14-AA release induced by TPA in CLA/C-14-AA pre-t reated cultures was significantly lower than cultures pre-treated with LA/C-14-AA. Furthermore, TPA-induced C-14-PGE(2) was significantly lo wer in cultures pre-treated with CLA/C-14-AA compared with cultures pr e-treated with LA/C-14-AA. The effects of LA and CLA on AA composition of phospholipids and subsequent arachidonate-derived PGE(2) synthesis will provide insight into the anti-promoter mechanisms of CLA. (C) 19 98 Elsevier Science Ireland Ltd.