Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HepG2 cell line is a valuable tool for screening for cytotoxicity in the early phase of pharmaceutical development. Some compounds which produce reactive and toxic metabolites, are classified as being toxic in HepG2 cells. In contrast, other compounds, which are toxic in primary human hepatocytes, are not toxic in HepG2 cells. A difference in metabolism between HepG2 cells and primary human hepatocytes might be the reason. To investigate this, cytochrome P450 and Phase II enzyme levels were characterized. In the present study the focus is on Phase II enzyme metabolism. Transcript levels of UDP-glucuronosyl transferases (UGTs), sulfotransferases (SULTs), glutathione S-transferases (GSTs), N-acetyltransferase-1 (NAT1) and epoxide hydrolase (EPHX1) were measured with quantitative PCR in HepG2 cells and cryopreserved primary human hepatocytes. Levels of SULT1A1, 1A2, 1E1, 1A2, and 2A1, microsomal GST 1, GST mu1, NAT1, and EPHX1 in HepG2 cells were almost similar to levels in primary human hepatocytes. In contrast, levels of UGT1A1 and 1A6 transcripts were between 10- and more than 1000-fold higher in the primary hepatocytes. The regulatory processes of Phase II enzymes by the aryl hydrocarbon receptor, pregnane X receptor and constitutive androstane receptor were studied in HepG2 cells and appeared quite similar to those in primary human hepatocytes. Due to the involvement of Phase II enzymes in the toxication of some compounds, HepG2 cells can be a valuable cellular system to predict toxicity for these compounds. On the other hand, the normal expression of most Phase II enzymes in combination with the lower expression of cytochrome P450 enzymes in HepG2 cells might result in an underestimation of toxicity for several compounds. Compared to primary human hepatocytes, HepG2 cells are a relatively easy-to-handle tool to study the up-regulation of Phase II enzymes.
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PMID:Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. 1771 55

Aromatic amine components in hair dyes and polymorphisms in genes that encode enzymes responsible for hair dye metabolism may be related to bladder cancer risk. We evaluated the association between hair dye use and bladder cancer risk and effect modification by N-acetyltransferase-1 (NAT1), NAT2, glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) genotypes in a population-based case-control study of 1193 incident cases and 1418 controls from Maine, Vermont and New Hampshire enrolled between 2001 and 2004. Individuals were interviewed in person using a computer-assisted personal interview to assess hair dye use and information on potential confounders and effect modifiers. No overall association between age at first use, year of first use, type of product, color, duration or number of applications of hair dyes and bladder cancer among women or men was apparent, but increased risks were observed in certain subgroups. Women who used permanent dyes and had a college degree, a marker of socioeconomic status, had an increased risk of bladder cancer [odds ratio (OR) = 3.3, 95% confidence interval (CI): 1.2-8.9]. Among these women, we found an increased risk of bladder cancer among exclusive users of permanent hair dyes who had NAT2 slow acetylation phenotype (OR = 7.3, 95% CI: 1.6-32.6) compared to never users of dye with NAT2 rapid/intermediate acetylation phenotype. Although we found no relation between hair dye use and bladder cancer risk in women overall, we detected evidence of associations and gene-environment interaction with permanent hair dye use; however, this was limited to educated women. These results need confirmation with larger numbers, requiring pooling data from multiple studies.
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PMID:Hair dye use and risk of bladder cancer in the New England bladder cancer study. 2167 99