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HERO ID
4931394
Reference Type
Journal Article
Subtype
Review
Title
Nephrocarcinogenic Xenobiotics
Author(s)
Henschler, D; Dekant, W
Year
1990
Is Peer Reviewed?
1
Journal
Toxicology Letters
ISSN:
0378-4274
EISSN:
1879-3169
Volume
53
Issue
1-2
Page Numbers
105-110
Language
English
PMID
2219148
DOI
10.1016/0378-4274(90)90102-r
Abstract
A review was presented that concentrated on those nephrocarcinogens where the molecular mechanisms have been fully elucidated or have been based on valid hypotheses. Intensive studies have been performed to clarify the mechanism of haloalkene induced nephrotoxicity and carcinogenicity. The conjugation of the haloalkene with glutathione and processing of the glutathione conjugate followed by formation of reactive intermediates catalyzed by cysteine conjugate beta-lyase were noted to be most probably involved in tumor induction in the kidney observed with trichloroethene (79016), hexachlorobutadiene (87683) and dichloroacetylene (7572294). Formation of toxic S-conjugates, most probably catalyzed by renal glutathione-S-transferases, was indicated to possible by involved in the renal carcinogenesis of tris-2,3-dibromopropylphosphate in rats. Under certain conditions of application, nitrosamines have induced high yields of renal tubular carcinoma. Some metals and metal complexes have also induced renal tumors. A variety of xenobiotics (notably petroleum hydrocarbons, limonene (7705148) and related structures such as 1,4-dichlorobenzene (106467) have caused renal tumors exclusively in the male rat. The iron complex of nitrolotriacetic-acid was a renal carcinogen in rats and mice when given at high doses. Potassium-bromate (7758012) was a renal carcinogen in rats. Certain 5-nitrofurans have also been noted to cause renal cell carcinomas. Chronic abuse of acetaminophen (103902) and phenacetin (62442) has also been associated with human urothelial neoplasia. The authors conclude that with many of the known renal carcinogens the data on genotoxicity and mutagenicity are inconsistent, causing a major problem in risk assessment.
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