title: Urinary N3 adenine DNA adducts in humans occupationally exposed to styrene.
abstract: 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.
authors.affiliation: Apigenex, Podebradská 186, CZ-180 66 Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Mikes
authors.forename: Marek
authors.initials: M
authors.lastname: Korínek
authors.forename: Igor
authors.initials: I
authors.lastname: Linhart
authors.forename: Jan
authors.initials: J
authors.lastname: Krouzelka
authors.forename: Ludmila
authors.initials: L
authors.lastname: Dabrowská
authors.forename: Vladimír
authors.initials: V
authors.lastname: Stránský
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mráz
mesh_terms: D000225:Adenine / Q000737:chemistry*; D015415:Biomarkers / Q000652:urine; D018736:DNA Adducts / Q000652:urine*; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D016273:Occupational Exposure / Q000009:adverse effects*; D020058:Styrene / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D020058:Styrene; D000225:Adenine