Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-Hodgkin's lymphomas (NHL) are one of the most chemosensitive human malignancies. Complete response (CR) is often achieved, but many patients relapse and a second CR is difficult to obtain because of the development of chemoresistance. In an attempt to better understand the biology and the chemosensitivity of these lymphoid tumors, we assessed the main drug-metabolizing enzyme systems in normal lymphocytes, chemosensitive NHL and chemoresistant NHL. Cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, -mu, -pi) were assayed by immunoblotting. UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, sulfatase, GST activity, and glutathione (GSH) content, were determined by spectral assays. Results showed the absence of all probed cytochromes P-450 in normal lymphocytes and NHL cells tested. GST activity was significantly lower in chemoresistant NHL compared to normal lymphocytes. GST-alpha was not detected in either normal lymphocytes or NHL cells. GST-pi was the predominant isoenzyme, and GST-mu was not detected in chemosensitive NHL. GSH content was significantly lower in chemoresistant NHL compared to other lymphoid tissues tested. The conjugating enzymes UDP-glucuronosyltransferase and sulfatase were similar in either chemoresistant NHL compared to chemosensitive NHL. The activity of the hydrolytic enzyme beta-glucuronidase was lower in chemoresistant compared to chemosensitive NHL, whereas sulfatase was higher in sensitive NHL compared to normal lymphocytes. Epoxide hydrolase was not detected in either normal or NHL cells tested. In conclusion, these studies did not show any cytochrome P-450 in human lymphoid cells tested, but pointed out noteworthy differences for other enzyme systems tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Main drug-metabolizing enzyme systems in human non-Hodgkin's lymphomas sensitive or resistant to chemotherapy. 853 97

Considering the role in the metabolism of chemicals played by biotransformation enzymes, we aimed at determining whether any association exists between genetic polymorphisms in CYP1A1, CYP2E1, epoxide hydrolase (EPHX), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to lymphomas. PCR-RFLP-based genotyping assays were used to determine the frequency of polymorphisms in CYP1A1 (3'-flanking region), CYP2E1 (5'-flanking region and intron 6), EPHX (exons 3 and 4), GSTM1 (deletion), GSTP1 (exon 5) and GSTT1 (deletion) in a case-control study comprised of 219 patients with morbus Hodgkin (MH) and non-Hodgkin's lymphomas (NHL) and 455 age- and sex-matched healthy individuals. The distribution of genotypes in CYP2E1-intron 6 was significantly different between the control group and all lymphomas (P = 0.03), patients with NHL (P = 0.024), and especially aggressive diffuse NHL (P = 0.007). Grading of NHL seemed to be associated with this polymorphism as well (P = 0.041). The EPHX-exon 3 genotype distribution was significantly different between control males and males with all lymphomas (P = 0.01) or with NHL (P = 0.019). The Val/Val genotype of GSTP1-exon 5 was prevalent in all MH [odds ratio (OR) = 2.08, 95% confidence interval (CI) = 1.05-4.14] and this difference was particularly evident in females (OR = 2.97, 95% CI = 1.16-7.61). A significant difference in the distribution of GSTP1-exon 5 genotypes was found between NHL tumors >5 cm and those <5 cm (P = 0.03). The results suggest that genetic polymorphisms of biotransformation enzymes may play a significant role in the development of lymphoid malignancies.
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PMID:Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas. 1140 8