Academic Journal
Quantification of DNA and hemoglobin adducts of 3,4-epoxy-1,2-butanediol in rodents exposed to 3-butene-1,2-diol
| Title: | Quantification of DNA and hemoglobin adducts of 3,4-epoxy-1,2-butanediol in rodents exposed to 3-butene-1,2-diol |
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| Authors: | Powley, M. W., Li, Y., Upton, P. B., Walker, V. E., Swenberg, J. A. |
| Publisher Information: | Oxford University Press |
| Publication Year: | 2005 |
| Collection: | HighWire Press (Stanford University) |
| Subject Terms: | MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
| Description: | 1,3-butadiene (BD) is a confirmed rodent carcinogen and a suspect human carcinogen that forms mutagenic epoxide metabolites during biotransformation. Species differences in the roles of individual DNA reactive intermediates in BD mutagenicity and carcinogenicity are not completely understood. Evidence suggests that 1,2:3,4-diepoxybutane (DEB) is responsible for the mutagenic effect induced by exposures to low concentrations of BD in mice and that metabolites of 3-butene-1,2-diol (BD-diol) are involved in the mutagenicity at high exposures in both mice and rats. Two reactive metabolites, 3,4-epoxy-1,2-butanediol (EB-diol) and hydroxymethylvinyl ketone (HMVK), are formed during the biotransformation of BD-diol and could potentially be involved in BD-diol associated mutagenicity. To examine the role of EB-diol in BD-diol mutagenicity we have evaluated the dosimetry of N 7-(2,3,4-trihydroxybutyl)guanine (THB-Gua) and N -(1,2,3-trihydroxybutyl)valine (THB-Val) in female B6C3F1 mice and female F344 rats exposed by inhalation to 0, 6, 18, and 36 ppm BD-diol for 4 weeks (6 hr/day x 5 days/week). Results showed that mice had higher levels of both THB-Gua and THB-Val than rats. An evaluation of THB-Gua adducts showed virtually no differences between liver and lung for either species, suggesting that EB-diol is stable and freely circulates. The data also indicated that THB adduct formation began to plateau around 18 ppm in both species. Most importantly, the shape of the dose-response curve for THB adduct formation mimicked that observed for hypoxanthine-guanine phosphoribosyltransferase ( Hprt) mutation frequency. This showed that THB adducts, while not thought to be responsible for causing the mutations, are good quantitative indicators of mutagenicity in rodents exposed to BD-diol. Although the potential contribution of HMVK still needs to be evaluated, the data suggest that EB-diol is responsible, at least in part, for BD-diol associated mutagenicity in rodents. |
| Document Type: | text |
| File Description: | text/html |
| Language: | English |
| Relation: | http://carcin.oxfordjournals.org/cgi/content/short/bgi119v1; http://dx.doi.org/10.1093/carcin/bgi119 |
| DOI: | 10.1093/carcin/bgi119 |
| Availability: | https://doi.org/10.1093/carcin/bgi119 http://carcin.oxfordjournals.org/cgi/content/short/bgi119v1 |
| Rights: | Copyright (C) 2005, Oxford University Press |
| Accession Number: | edsbas.AF07C362 |
| Database: | BASE |
| Description not available. |