EFFECTS OF 9 MUTAGENIC PYROLYSATES, 5 FOODSTUFFS, 4 ANTI-TUMOR DRUGS AND 6 HEAVY METALS IN A TWO-STAGE MOUSE SKIN MODEL
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Nine mutagenic heterocyclic amines, 5 foodstuffs, and 4 anti-tumor drugs were tested for tumor initiating activity in a two stage skin carcinogenesis model using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as the promoter. All compounds were topically applied twice weekly for 5 weeks on the dorsal skin, and then followed by similar TPA administration for 47 weeks. Test chemical groups with TPA promotion induced skin tumors in 5 to 35% of the mice, wheter no tumors appeared in the groups treated with test chemicals alone or TPA alone. Statistical analysis according to either Fisher exact test or Peto trend test revealed significant differences for tumor appearance in the Trp-P-1, Trp-P-2, MeAαC, Phe-P-1, AF-2, and BHA followed by TPA groups as compared to the TPA alone. Zinc Chloride, chromic chloride, cadmium chloride, nickel chloride, mercuric chloride, and arsenic acid were tested for possible tumor promoting activity in the skin of emale SENCAR mice pretreated with 7, 12-dimethylbenz (a) anthracene (DMBA). At a dose of 200 μg applied twice weekly for 26 weeks, none of the metal compounds tested enhanced skin tumor development. They also showed no tumor-developing potency when continuously applied in the smae manner without DMBA initiation. The results indicated that Trp-P-2 and AF-2 have an initiating activity, and Trp-P-1, MeAαC, Phe-P-1 and BHA show possible initiating potency in two-stage mouse skin model, but the heavy metal compounds tested do not have any tumor-promoting or tumorigenic activity in the mouse skin.
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日本毒性病理学会 | 論文
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