Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Radical oxidation of DNA gives rise to potentially deleterious lesions such as strand breaks and various nucleobase modifications including 5-formyl-2'-deoxyuridine (5-fo-dU), a prevalent product derived from the oxidation of the C5-methyl group of thymidine. The present study investigates the unusual transformation of 5-fo-dU into 5-hydroxy-2'-deoxyuridine (5-oh-dU) and 5,6-dihydroxy-5,6-dihydro-2'-deoxuridine (gly-dU), two products typically associated with the oxidation of 2'-deoxycytidine. Detailed mechanistic analyses reveal that hydrogen peroxide, either generated as a byproduct of ascorbate autoxidation or added exogenously, mediates the formation of these oxidatively induced C5-dealkylated products. We show that the major product 5-oh-dU results from a Baeyer-Villiger rearrangement of the formyl functionality of 5-fo-dU while the minor product gly-dU derives from α,β-oxidation of the enal portion followed by deformylation. These reactions were observed in both 2'-deoxynucleoside monomers as well as isolated DNA. Our findings further clarify the oxidation chemistry of thymidine and highlight a novel oxidative decomposition pathway that can help understand the fate of certain types of DNA damage. Furthermore, our results underscore the pro-oxidant properties of ascorbate that can lead to the adventitious oxidation of substrates via the reduction of trace metals ions and generation of hydrogen peroxide.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1021/acs.chemrestox.4c00410 | DOI Listing |
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