Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues : factors influencing renal carcinogenesis induced by xenobiotics

Delbanco, E. H., Bolt, H. M., Huber, W. W., Beken, S., Geller, F., Philippou, S., Brands, F. H., Brüning, T., & Thier, R. (2001) Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues : factors influencing renal carcinogenesis induced by xenobiotics. Archives of Toxicology, 74(11), pp. 688-694.

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Abstract

In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugatiton with glutathione. It has mostly been assamed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST θ); 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole for GST α; 1,2-dichloro-4-nitro-benzene for GST μ; ethacrynic acid and 4-vinylpyridine for GST π; and methyl chloride for GST θ. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

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ID Code: 77451
Item Type: Journal Article
Refereed: Yes
Keywords: Genotyping, Glutathione transferases, Kidney tissue, Phenotyping, Renal carcinomas, 1 chloro 2, 4 dinitrobenzene, 1, 2 dichloro 4 nitrobenzene, 4 chloro 7 nitrobenzofurazan, 4 vinylpyridine, chlorinated hydrocarbon, etacrynic acid, glutathione, glutathione transferase, methyl chloride, xenobiotic agent, adult, age, aged, article, cancer staging, carcinogenesis, clinical article, controlled study, drug conjugation, enzyme activity, enzyme specificity, enzyme substrate complex, female, gender, genetic polymorphism, genotype, human, human tissue, kidney carcinoma, liver, male, phenotype, priority journal, toxicokinetics, Carcinoma, Renal Cell, Dinitrochlorobenzene, DNA, Neoplasm, Humans, Isoenzymes, Kidney, Kidney Neoplasms, Middle Aged, Serine Endopeptidases
DOI: 10.1007/s002040000184
ISSN: 0340-5761
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Schools > School of Early Childhood & Inclusive Education
Copyright Owner: Copyright 2001 Springer
Deposited On: 17 Oct 2014 00:37
Last Modified: 17 Oct 2014 00:37

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