title: Inactivity of fecapentaene-12 as a rodent carcinogen or tumor initiator.
abstract: The possible carcinogenic activity of synthetic fecapentaene-12 (FP-12) was studied in several mammalian test systems: (a) for carcinogenicity by intrarectal instillation in male F344/NCr rats as well as by intrarectal and subcutaneous application in male B6C3F1 mice; (b) for initiation by skin painting in female SENCAR mice followed by repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), with 7,12-dimethylbenz[a]anthracene (DMBA) followed by TPA as positive control; (c) in a rat subcutaneous granuloma pouch assay in which mutagenicity was measured by induction of 6-thioguanine (6-TG) resistance and carcinogenicity was determined by induction of subcutaneous tumors in the pouch. There was no significant increase in tumor incidence after 72-78 weeks in test (a), although 2 rats receiving FP-12 intrarectally developed colon polyps. FP-12 did not initiate any skin tumors in test (b), nor did it significantly convert DMBA-initiated papillomas into carcinomas when 8 of the positive control mice were given FP-12 weekly for 10 weeks after 10 weeks on the DMBA-TPA regimen. Although FP-12 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were comparably mutagenic in test (c), FP-12 induced no tumors after more than a year in 133 rats at risk while MNNG induced 7 tumors in 107 rats. These rodent assays provide no evidence that FP-12 is a strong carcinogen, although the possibility remains that it may possess weak carcinogenic activity not revealed by these experiments.
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D003111:Colonic Polyps / Q000139:chemically induced; D005260:Female; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens; D010212:Papilloma / Q000139:chemically induced; D011090:Polyenes / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; D009153:Mutagens; D011090:Polyenes; D008769:Methylnitronitrosoguanidine; D015127:9,10-Dimethyl-1,2-benzanthracene; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene; D013755:Tetradecanoylphorbol Acetate