Mechanism of mouse skin tumor promotion by n-dodecane.
Application of the alkane n-dodecane to the dorsal skin of 6-8 week old female SENCAR mice initiated with 10 nmol dimethylbenz[a]anthracene led to papilloma formation in the majority of treated animals. Compared to the potent phorbol diester 12-O-tetradecanoylphorbol-13-acetate (TPA), n-dodecane was several orders of magnitude less potent on a dose basis, and maximal papilloma response required more extended application (22 weeks for 50 mg dodecane compared to 12 weeks for 2 micrograms TPA). In two-stage promotion experiments n-dodecane appeared to act as a stage II promoting agent at appropriate doses, being comparable in activity to mezerein--an agent with well-characterized activity of this type. Dodecane, unlike mezerein, did not induce the formation of a significant number of pyknotic cells, however, suggesting that the weak promoting activity of dodecane in stage 1 was not a result of toxicity. In comparison with TPA, both mezerein and n-dodecane at promoting doses induced less sustained hyperplasia in SENCAR mouse skin, a finding also consistent with the proposal that n-dodecane is principally active in stage II of two-stage promotion models. Both agents induced ornithine decarboxylase activity in SENCAR mouse skin, the maximal induction being observed at apparently the same time after a single application.
Baxter
C S
CS
Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056.
Miller
M L
ML
D000096:Acetone; D000473:Alkanes; D000818:Animals; D003043:Cocarcinogenesis; D004224:Diterpenes; D005260:Female; D051379:Mice; D010212:Papilloma / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced*; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate
D000473:Alkanes; D004224:Diterpenes; D013729:Terpenes; C007548:n-dodecane; D000096:Acetone; C011309:mezerein; D013755:Tetradecanoylphorbol Acetate