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Individual phenotypes with respect to drug response or toxicity often result from genetic variations that alter drug metabolism. We have been focusing on genomic loci that encode various enzymes and transporters involved in the metabolism of drugs, and have described more than 1200 single-nucleotide polymorphisms (SNPs) and other variations. Regarding the carbohydrate sulfotransferase (CHST) gene family, we have already constructed high-density SNP maps of three genomic segments that included CHST2, CHST4, and CHST5, providing a total of 28 SNPs for those loci. In the present study, we screened DNA from 48 healthy Japanese volunteers for SNPs at the CHST1 and CHST3 gene loci, by means of direct sequencing combined with a polymerase chain reaction method for amplifying genomic DNA, and characterized 77 SNPs and four insertion–deletion polymorphisms. The collection of human variations presented here adds to the archive of tools now available for investigating complex genetic diseases, population migration patterns, and a variety of pharmacogenetic possibilities. [ABSTRACT FROM AUTHOR]

2-Aminophenoxazine-3-one (Phx-3) induced cellular apoptosis in mouse melanoma B16 cells as detected by DNA laddering and upregulated Fas expression in the cells in vitro. Next, the anti-metastatic effects of Phx-3 were investigated in C56BL/6 mice. When B16 melanoma cells were injected into the tail veins of mice, significant metastasis of the cells was indicated in the lungs, 14 days after treatment. In contrast, when 0.5 mg/kg Phx-3 was administered to mice through the tail veins, once simultaneously with or every three days after the administration of B16 melanoma cells, the number of metastasized pulmonary cells was extremely reduced. Moderate reduction of the number of metastasized pulmonary cells was indicated in the mice with a single dose of Phx-3 on day 3 after injection of the cells. However, when Phx-3 was administered in a single dose, 6 or 9 days after the injection of the cells, the number of metastasized pulmonary cells remained the same. The present results indicate that the metastasis of mouse B16 melanoma cells to the lung was significantly inhibited in mice administered Phx-3, which activated the intrinsic and extrinsic apoptotic pathways. The present study suggests that Phx-3 might be a potential anti-metastatic agent as well as an anticancer agent.