Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
The environmental pollutant 6-nitrochrysene (6-NC) is a powerful mammary carcinogen and mutagen in rats. Our previous studies have shown that 6-NC is metabolized to trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (1,2-DHD-6-NC) in rats and in several in vitro systems, including human breast tissue, and the latter is the proximate carcinogenic form in the rat mammary gland. Because optically active enantiomers of numerous polynuclear aromatic hydrocarbon (PAH) metabolites including chrysene have different biological activities, we hypothesized that the stereochemical course of 6-NC metabolism might play a significant role in the carcinogenic/mutagenic activities of the parent 6-NC. The goal of this study is to evaluate the effect of stereochemistry on the mutagenicity of 1,2-DHD-6-NC using the cII gene of lacI mammary epithelial cells in vitro. Resolution of (+/-)-1,2-DHD-6-NC was obtained by either nonchiral or chiral stationary phase HPLC methods. We determined that the ratio of (-)-[R,R]- and (+)-[S,S]-1,2-DHD-6-NC formed in the metabolism of 6-NC by rat liver microsomes is 88:12. The mutation fractions and mutation spectra of [R,R] and [S,S]-enantiomers were examined. Our results showed that the [R,R]-isomer is a significantly (p < 0.01) more potent mutagen than the [S,S]-isomer. The major types of mutation induced by the [R,R]-enantiomer are AT > GC, AT > TA, and GC > TA substitutions, and these are similar to those obtained from 6-NC in vivo in the mammary glands of rats treated with 6-NC. The mutation spectra of the [S,S]-isomer were similar to the [R,R]-isomer, but a higher percentage of AT > GC substitutions in the [R,R]-isomer was noted. On the basis of the results of the present study, we hypothesize that [R,R]-1,2-DHD-6-NC is the proximate carcinogen of 6-NC in the rat mammary gland in vivo and will test this hypothesis in a future study.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818434 | PMC |
http://dx.doi.org/10.1021/tx9002897 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!