Reducing substrate activity of some aromatic amines for prostaglandin H synthase

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Abstract
An inbred strain of SENCAR mice was developed that is more sensitive to two-stage skin carcinogenesis protocols than the outbred parental stock. These mice, registered as SSIN/UTSP, were compared to the SENCAR in initiation-promotion pro-tocols using the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 22 weeks at dose levels of 0.5, 1.0 and 2.0 μg. With 0.5 μg of TPA, the number of papillomas in the SSLN was 3-fold higher than in the SEN CAR; the tumor incidence was 100 versus 60%, respectively. Similar, although less dramatic, results were found with 1.0 and 2.0 μg of TPA. In two-step promotion protocols using TPA twice weekly for 2 weeks and 2 μg mezerein twice weekly for 15 weeks the SSIN produced −50% more tumors than the SENCAR at 0.5 μg of TPA. At 2 μg of TPA the tumor response between the two mice was not significantly different. Epidermal hyperplasia was considerably greater in the SSIN at 0.5 μg of TPA as was ornithine decarboxylase activity. These TPA-sensitive inbred mice should be useful in investiga tions on the biochemical and genetic factors involved in skin tumor promotion.