Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.67 (thiopurine methyltransferase)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Environmental chemicals may be involved in the etiology of breast cancer. Among them, organophosphorous compounds are the most widely used pesticides because of their extensive use in agriculture, medicine and industry. The risk of breast cancer is associated with prolonged exposure to female hormones and is attributed to estrogen since prolonged stimulation by steroid hormones may increase cell division. The aim of the present study was to identify the differentially expressed genes encoding enzymes that are important to drug transport and metabolism in parathion- and estrogen-treated human breast epithelial cell lines using cDNA microarrays. MCF-l0F, an immortalized human breast epithelial cell line was treated with parathion and estrogen, either alone or in combination, and malignant cells were developed through a series of sequential steps. Differential expression from the drug metabolism gene array showed that 17 genes were found to be altered either by parathion or estrogen alone, or the combination of both. Among the genes altered by parathion in comparison to the control were CHST5, CHST6 and CHST7 (sulfotransferases); CYP2F1, CYP3A7 and CYP4F3 (CYPs); GSTP1, GSTT2 and MGST1 (GSTs); MT1X (metallothionein); TPMT (methyltransferase); UGT1A1 and UGT2B (UDP glycosyltransferases). The same genes were down-regulated in estrogen alone including several metallothioneins (MT1A, MT1E, MT1H, MT1L and MT2A). The combination of parathion and estrogen induced down-regulation of three sulfotransferases, CYP2F1 and CYP4F3, MGST1, all metallothioneins and TPMT genes. There was no change in CYP3A7, GSTP1, GSTT2, UGT1A1 and UGT2B genes in the presence of both substances. It can be concluded from this study that organophosphorous pesticides such as parathion in the presence of estradiol induced changes in human drug metabolism gene expression in breast cells.
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PMID:Human drug metabolism genes in parathion-and estrogen-treated breast cells. 1798 97

The Clinical Laboratory Improvement Amendments of 1988 require that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SOD2, TLR4, and TPMT were validated in a Clinical Laboratory Improvement Amendments-accredited laboratory. Because no known reference materials were available, existing DNA samples were used for the analytical validation studies. Pharmacogenetic testing methods developed here were shown to be accurate and 100% analytically sensitive and specific. Other Clinical Laboratory Improvement Amendments-accredited laboratories interested in offering pharmacogenetic testing for these genetic variants, related to genotype-guided therapy for oncology, could use these publicly available samples as reference materials when developing and validating new genetic tests or refining current assays.
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PMID:Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology. 3079 85