Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Brüning, T., Thier, R., & Bolt, H.M. (2002) Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered. Reviews on Environmental Health, 17(3), pp. 163-172.

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Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

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ID Code: 77449
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: alpha 1 microglobulin, biochemical marker, carcinogen, copper, explosive, glutathione transferase, toluene derivative, animal experiment, animal model, article, breast cancer, cancer cell, carcinogenicity, controlled study, environmental exposure, female, genotype, kidney cancer, kidney injury, kidney proximal tubule, liver cancer, male, malignant neoplastic disease, mining, mouse, nephrotoxicity, nonhuman, protein urine level, target organ, urogenital tract tumor, Animals, Carcinogens, Dinitrobenzenes, Germany, Humans, Kidney, Kidney Neoplasms, Mice, Mutagens, Occupational Exposure, Rats, Animalia
DOI: 10.1515/REVEH.2002.17.3.163
ISSN: 00487554 (ISSN)
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2002 Walter de Gruyter GmbH
Deposited On: 21 Oct 2014 02:58
Last Modified: 21 Oct 2014 02:58

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