Hereditary tyrosinemia type 1 metabolites impair DNA excision repair pathways.

Abstract

Hereditary tyrosinemia type 1 is an autosomal recessive metabolic disorder, which is caused by a defective fumarylacetoacetate hydrolase enzyme, and consequently metabolites such as succinylacetone and p-hydroxyphenylpyruvate accumulate. We used a modified comet assay to determine the effect of these metabolites on base- and nucleotide excision repair pathways. Our results indicate that the metabolites affected the repair mechanisms differently, since the metabolites had a bigger detrimental effect on BER than on NER.

• Authors: E van Dyk, A Steenkamp, G Koekemoer, P J Pretorius
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 401 Issue 1 Pg. 32-6 (Oct 08 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20828540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Heptanoates
• Phenylpyruvic Acids
• 4-hydroxyphenylpyruvic acid
• succinylacetone
• Hydrogen Peroxide

Topics

• Cell Line
• Comet Assay
• DNA Repair
• Heptanoates (metabolism)
• Humans
• Hydrogen Peroxide (toxicity)
• Phenylpyruvic Acids (metabolism)
• Tyrosinemias (genetics, metabolism)