| Attributes | Values |
|---|
| rdf:type
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| Description
| - Among numerous adducts formed by reaction of DNA with p-benzoquinone (p-BQ), an electrophilic metabolite of benzene, only N2-(4-hydroxyphenyl)guanine (N2HPG) has been confirmed in vivo. If excreted in urine N2HPG would be a candidate non-invasive biomarker of the DNA damage caused by benzene. To test this hypothesis, biotransformation of N2HPG was studied in rats. Unchanged N2HPG in urine amounted to 8.0 ? 2.2 % and 9.1 ? 1.7 % (mean SE) at the dose of 2 mg/kg excreted within 1 and 2 days after ip dosage, respectively. After acidic hydrolysis of the urine a slight but consistent increase in urinary N2HPG to 9.5 ? 3.2 % and 11 ? 2.6 % of dose was found within 1 and 2 days, respectively, indicating formation of hydrolysable conjugates. An oxidised metabolite was detected by LC-ESI-MS and identified by comparison with authentic standard as N2-(4-hydroxyphenyl)-8-oxoguanine (N2HPOG). Its excretion amounted to 2.7 ? 0.2 % of dose and increased to 12.0 ? 2.7 % of dose when N2HPOG was released from its conjugates by acidic hydrolysis. Glucuronides and sulphates of both N2HPG and N2HPOG were confirmed in urine by LC-ESI-MS and by enzymatic treatment with glucuronidase/sulphatase. These results indicate an extensive metabolism of N2HPG in vivo, which must be taken into account when considering N2HPG as a possible biomarker of exposure to benzene.
- Among numerous adducts formed by reaction of DNA with p-benzoquinone (p-BQ), an electrophilic metabolite of benzene, only N2-(4-hydroxyphenyl)guanine (N2HPG) has been confirmed in vivo. If excreted in urine N2HPG would be a candidate non-invasive biomarker of the DNA damage caused by benzene. To test this hypothesis, biotransformation of N2HPG was studied in rats. Unchanged N2HPG in urine amounted to 8.0 ? 2.2 % and 9.1 ? 1.7 % (mean SE) at the dose of 2 mg/kg excreted within 1 and 2 days after ip dosage, respectively. After acidic hydrolysis of the urine a slight but consistent increase in urinary N2HPG to 9.5 ? 3.2 % and 11 ? 2.6 % of dose was found within 1 and 2 days, respectively, indicating formation of hydrolysable conjugates. An oxidised metabolite was detected by LC-ESI-MS and identified by comparison with authentic standard as N2-(4-hydroxyphenyl)-8-oxoguanine (N2HPOG). Its excretion amounted to 2.7 ? 0.2 % of dose and increased to 12.0 ? 2.7 % of dose when N2HPOG was released from its conjugates by acidic hydrolysis. Glucuronides and sulphates of both N2HPG and N2HPOG were confirmed in urine by LC-ESI-MS and by enzymatic treatment with glucuronidase/sulphatase. These results indicate an extensive metabolism of N2HPG in vivo, which must be taken into account when considering N2HPG as a possible biomarker of exposure to benzene. (en)
|
| Title
| - Metabolism of N2-(4-Hydroxyphenyl)guanine, a DNA Adduct Formed from p-Benzoquinone, in Rat
- Metabolism of N2-(4-Hydroxyphenyl)guanine, a DNA Adduct Formed from p-Benzoquinone, in Rat (en)
|
| skos:prefLabel
| - Metabolism of N2-(4-Hydroxyphenyl)guanine, a DNA Adduct Formed from p-Benzoquinone, in Rat
- Metabolism of N2-(4-Hydroxyphenyl)guanine, a DNA Adduct Formed from p-Benzoquinone, in Rat (en)
|
| skos:notation
| - RIV/60461373:22310/11:43881495!RIV12-MSM-22310___
|
| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| - P(2B08051), Z(MSM6046137301)
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| http://linked.open...iv/cisloPeriodika
| |
| http://linked.open...vai/riv/dodaniDat
| |
| http://linked.open...aciTvurceVysledku
| |
| http://linked.open.../riv/druhVysledku
| |
| http://linked.open...iv/duvernostUdaju
| |
| http://linked.open...titaPredkladatele
| |
| http://linked.open...dnocenehoVysledku
| |
| http://linked.open...ai/riv/idVysledku
| - RIV/60461373:22310/11:43881495
|
| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - molecular dosimetry; biotransformation; DNA adducts; p-benzoquinone; benzene (en)
|
| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| |
| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| |
| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Mikeš, Petr
- Frantík, Emil
- Linhart, Igor
- Mráz, Jaroslav
- Králík, Antonín
|
| http://linked.open...ain/vavai/riv/wos
| |
| http://linked.open...n/vavai/riv/zamer
| |
| issn
| |
| number of pages
| |
| http://bibframe.org/vocab/doi
| - 10.1016/j.toxlet.2011.06.016
|
| http://localhost/t...ganizacniJednotka
| |
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