The first stage and complete promoting activity of retinoic acid but not the analog RO-10-9359.
Retinoic acid has the ability to act as either a weak first stage promoter or a weak complete promoter in the initiation-promotion protocol for skin carcinogenesis in the SENCAR mouse. The retinoid analog RO-10-9359 lacks this tumor promoting activity. Both retinoids however inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Additional comparisons revealed that retinoic acid alone can induce dark keratinocytes, a characteristic of tumor promoters, while RO-10-9359 cannot. Retinoic acid but not RO-10-9359 can induce an immediate chemiluminescence response in human polymorphonuclear cells. Both retinoids, however, inhibit a TPA-induced response. Since the chemiluminescence response is believed to be due to oxygen free radical generation, the data suggest that the ability of retinoic acid but not RO-10-9359 to promote tumors and induce dark cells may be due to initial oxidative reactions at the cell membrane.
Fischer
S M
SM
Klein-Szanto
A J
AJ
Adams
L M
LM
Slaga
T J
TJ
D000818:Animals; D005050:Etretinate / Q000633:toxicity*; D005260:Female; D007633:Keratins / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D014212:Tretinoin / Q000633:toxicity*
D014212:Tretinoin; D005050:Etretinate; D007633:Keratins; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate