JB6 murine epidermal cell lines sensitive and resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation exhibit differential arachidonic acid metabolism in response to TPA and the calcium ionophore A23187.
In a study of arachidonic acid metabolism in murine epidermal JB6 cells, promoter-sensitive (P+) and promoter-resistant (P-) variants, labeled with [3H]arachidonic acid, were treated successively with 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. Released radiolabel was separated by HPLC and identified by coelution of standards. Prostacyclin release was then quantified by radioimmunoassay for 6-keto prostaglandin (PG)F1 alpha. A23187 alone resulted in a small but significant enhanced release of radiolabel from both cell variants (0.7 +/- 0.2% for P- and 0.6 +/- 0.3% for P+ cells; mean +/- SD). Treatment with TPA and subsequent treatment with A23187 resulted in a synergistically enhanced release of radiolabel from both cell variants (4.1 +/- 0.8% for P- and 3.4 +/- 0.9% for P+ cells) relative to that with either agent alone. Although the predominant product for each treatment regimen was prostaglandin E2 (PGE2), the TPA-resistant cells (P-) released significantly more 6-keto PGF1 alpha, a stable breakdown product of PGI2, than did the TPA-sensitive (P+) cells. These results indicate differential arachidonic acid metabolism between JB6 cell variants resistant and sensitive to TPA-induced transformation.
Smith
J S
JS
Department of Environmental Health, University of Cincinnati College of Medicine, OH 45267-0056.
Wey
H E
HE
Leikauf
G D
GD
Baxter
C S
CS
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002460:Cell Line; D002461:Cell Line, Transformed / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000378:metabolism*; D004351:Drug Resistance; D011464:Epoprostenol / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D011863:Radioimmunoassay; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate