Fatty acid modification of C3H 10T 1/2 fibroblast cells: changes in benzo(a)pyrene metabolism and phorbol ester binding.
The mouse embryo fibroblast cell line, C3H 10T 1/2 Cl8, was studied as an in vitro experimental model to investigate the mechanism and specificity behind the modulation of carcinogenesis by dietary lipid. The cells were grown in medium supplemented with 95 microM stearate, linoleate, or palmitate as fatty acid/albumin complexes, during which time they maintained normal growth and morphology characteristics. After 5 days of supplementation total cellular lipid fatty acid was enriched in the supplemented fatty acid. By Day 40, however, fatty acid profiles of all groups were the same. Cellular uptake and utilization of 14C-radiolabeled fatty acids were measured. Within 24 h of supplementation, label was incorporated into cholesterol and diglycerides, cholesterol ester, alkyldiacylglycerols, and phospholipids. Approximately half of the radiolabel was found in phosphatidylcholine. Supplementation significantly increased the rate of benzo(a)pyrene metabolism, but did not affect DNA modification by benzo(a)pyrene. Phorbol dibutyrate binding to C3H 10T 1/2 cells at 4 degrees C was modified by lipid supplementation. At 37 degrees C and 23 degrees C, phorbol dibutyrate binding was characterized by both high- and low-affinity sites for linoleate- and stearate-supplemented cells. At 4 degrees C high-affinity binding was absent in stearate- and palmitate-supplemented cells, but was maintained in linoleate-supplemented cells. These studies suggest that the unsaturated fatty acid content of the diet may not significantly affect the initiation stage of benzo(a)pyrene carcinogenesis, but may instead affect promotion. One possible mechanism for this could involve changes in the lipid microenvironment of membrane receptors involved in tumor promotion.
Matsui
M S
MS
Jeffrey
A M
AM
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002460:Cell Line; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy
D005227:Fatty Acids; D010703:Phorbol Esters; D001564:Benzo(a)pyrene; D015240:Phorbol 12,13-Dibutyrate