Initiating activity in a two-stage mouse skin model of nine mutagenic pyrolysates of amino acids, soybean globulin and proteinaceous food.
Trp-P-1, Trp-P-2, MeA alpha C, A alpha C, Glu-P-1, Glu-P-2, Lys-P-1, IQ and Phe-P-1 were tested for tumour initiating activity in a two-stage skin carcinogenesis model using 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The total initiating doses were 20 mg for Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2, 40 mg for MeA alpha C and A alpha C, 5 mg for Lys-P-1, 7.5 mg for IQ and 100 mg for Phe-P-1. 7,12-Dimethylbenz[a]anthracene was used as a positive control compound at a total dose of 100 micrograms. All compounds were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by similar TPA administration for 47 weeks. Trp-P-2 induced skin tumours in 30% of the mice (0.35 tumours/mouse), and Trp-P-1, MeA alpha C and Phe-P-1 in 10-20% (0.20-0.25 tumours/mouse). The smaller amounts of Lys-P-1 and IQ applied induced tumours at an incidence of 10 and 5% respectively. No tumours appeared in the groups treated with test chemicals alone or TPA alone. Statistical analysis according to either the Fisher exact test or Peto trend test revealed significant differences for tumour appearance in the Trp-P-1, Trp-P-2, MeA alpha C and Phe-P-1 followed by TPA groups as compared with that given TPA alone. The data were used to generate ID50 (50% initiating dose) values for each of the compounds.
D000818:Animals; D002243:Carbolines / Q000633:toxicity; D005260:Female; D007093:Imidazoles / Q000633:toxicity; D051379:Mice; D009153:Mutagens; D011804:Quinolines / Q000633:toxicity; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate
D002243:Carbolines; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C017821:2-amino-3-methyl-9H-pyrido(2,3-b)indole; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; C023847:Glu-P-2; D013755:Tetradecanoylphorbol Acetate; C017822:2-amino-9H-pyrido(2,3-b)indole