Urinary N3 adenine DNA adducts in humans occupationally exposed to styrene
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20553827
DOI
10.1016/j.toxlet.2010.05.015
PII: S0378-4274(10)01532-8
Knihovny.cz E-resources
- MeSH
- Adenine chemistry MeSH
- DNA Adducts urine MeSH
- Biomarkers urine MeSH
- Humans MeSH
- Molecular Structure MeSH
- DNA Damage drug effects MeSH
- Occupational Exposure adverse effects MeSH
- Styrene adverse effects MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenine MeSH
- DNA Adducts MeSH
- Biomarkers MeSH
- Styrene MeSH
Urine samples from humans occupationally exposed to styrene, with mandelic acid levels ranging from 400 to 1145 mg/g creatinine and from 68 to 400mg/g creatinine for high and low exposure group, respectively, were analysed for N3 adenine DNA adducts, namely, 3-(2-hydroxy-1-phenylethyl)adenine (N3 alpha A) and 3-(2-hydroxy-2-phenylethyl)adenine (N3 beta A). A sensitive LC-ESI-MSMS method was developed with the limit of quantification of 1 pg/mL for both analytes. Peaks corresponding to N3 alpha A and/or N3 beta A were found in seven of nine end-of-shift samples of the high exposure group and in six of 19 end-of-shift samples of the low exposure group. Concentration of N3 alpha A+N3 beta A amounted to 2.8+/-1.6 pg/mL (mean+/-S.D.; n=9) and 1.8+/-1.3 pg/mL (mean+/-S.D.; n=19) in the high and low exposure group, respectively. Of other 10 samples taken the next morning after exposure, two contained low but quantifiable concentrations of N3 alpha A and none contained N3 beta A. However, interfering peaks were detected also in some control urine samples. Out of 22 controls, six and two samples contained peaks co-eluting with N3 alpha A and N3 beta A, respectively. Therefore, the method used was found insufficiently specific to be applicable for biological monitoring. Comparing the excretion of N3 alpha A+N3 beta A to that reported previously in mice it can be estimated that at the same absorbed dose, humans excreted not more than 1/30 of the amount of adenine adducts excreted by mice. As a consequence, the damage to DNA caused by styrene 7,8-oxide (SO), a reactive metabolite of styrene, appears to be much lower in humans than in mice.
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