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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
The biological interaction of cis- and trans-urocanic acid and DNA
D B Yarosh1, S D Gettings, L G Alas
1Applied Genetics Inc., Freeport, New York 11520.
Abstract:
The potential for the cis and trans isomers of urocanic acid to produce DNA damage was measured by assays for DNA binding (32P-postlabeling assay), for induction of DNA repair (unscheduled DNA synthesis assay) and induction of mutations (Salmonella typhimurium and Escherichia coli plate-incorporation assays). These assays did not detect any evidence of a direct effect of either isomer of urocanic acid on DNA over a wide range of concentrations. These results suggest that neither isomer of urocanic acid alone, nor ultraviolet-irradiation of either cis or trans-urocanic acid produces significant DNA damage under conditions that permit cell survival.
Insights
Neither cis nor trans urocanic acid isomers cause DNA damage or mutations, even with UV exposure. Studies using DNA binding, repair, and mutation assays found no evidence of urocanic acid
Area of Science:
- Biochemistry
- Molecular Biology
- Genotoxicology
Background:
- Urocanic acid (UCA) is a product of histidine metabolism found in the skin.
- Both cis and trans isomers of UCA exist, with potential implications for biological activity.
- Concerns exist regarding the genotoxic potential of UCA, particularly under UV irradiation.
Purpose of the Study:
- To investigate the potential of cis and trans urocanic acid isomers to induce DNA damage.
- To assess the genotoxic effects of UCA isomers using a battery of in vitro assays.
- To determine if UV irradiation of UCA isomers enhances DNA damage induction.
Main Methods:
- DNA binding assessed using the 32P-postlabeling assay.
- DNA repair induction measured by the unscheduled DNA synthesis (UDS) assay.
- Mutagenicity evaluated with Salmonella typhimurium and Escherichia coli plate-incorporation assays.
Main Results:
- No evidence of direct DNA binding by either UCA isomer was detected across a wide concentration range.
- Neither isomer induced DNA repair (UDS) or mutations in bacterial assays.
- UV irradiation of cis or trans UCA did not result in significant DNA damage under cell-surviving conditions.
Conclusions:
- Under the tested conditions, neither cis nor trans urocanic acid isomers exhibit direct genotoxicity.
- Urocanic acid does not appear to be a significant inducer of DNA damage or mutations, alone or when exposed to UV light.
- These findings suggest a low risk of urocanic acid-induced genotoxicity in biological systems.
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