RESUMO
We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials.
Assuntos
Arsênio/metabolismo , Arsenicais/urina , Glutationa Transferase/genética , Metiltransferases/genética , Polimorfismo Genético , Purina-Núcleosídeo Fosforilase/genética , Poluentes Químicos da Água/metabolismo , Adolescente , Adulto , Idoso , Arsênio/urina , Criança , Monitoramento Ambiental , Feminino , Genótipo , Humanos , Masculino , Metilação , México , Pessoa de Meia-Idade , Dados de Sequência Molecular , Poluentes Químicos da Água/urina , Abastecimento de ÁguaRESUMO
Antiangiogenic activity has been identified in an aqueous EtOH extract of Rabdosia rubescens, a component of the dietary supplement PC SPES. Bioassay-guided fractionation using a novel in vitro human endothelial cell-based assay for angiogenesis afforded the diterpenoids ponicidin (1) and oridonin (2), with significant antiangiogenic activity at subcytotoxic concentrations, suggesting that these constituents may strongly contribute to the demonstrated clinical efficacy of PC SPES as a treatment for advanced prostate cancer.
