Mikes Petr, Korínek Marek, Linhart Igor, Krouzelka Jan, Frantík Emil, Vodicková Ludmila, Neufussová Lenka
RE&D VUFB, Podebradská 186, CZ-180 66 Prague, Czech Republic.
Toxicol Lett. 2009 Jan 10;184(1):33-7. doi: 10.1016/j.toxlet.2008.10.010. Epub 2008 Oct 25.
New urinary adenine adducts, 3-(2-hydroxy-1-phenylethyl)adenine (N3alphaA), 3-(2-hydroxy-2-phenylethyl)adenine (N3betaA), were found in the urine of mice exposed to styrene vapour. These styrene 7,8-oxide derived adenine adducts as well as previously identified guanine adducts, 7-(2-hydroxy-1-phenylethyl)guanine (N7alphaG) and 7-(2-hydroxy-2-phenylethyl)guanine (N7betaG) were quantified by HPLC-ESI-MS(2) and the excretion profile during and after a repeated exposure to 600mg/m(3) or 1200mg/m(3) of styrene for 10 consecutive days (6h/day) was determined. The excretion was dose dependent. Total N3 adenine adducts (N3alphaA+N3betaA) excreted amounted to nearly 0.8x10(-5)% of the absorbed dose while urinary N7 guanine adducts (N7alphaG+N7betaG) amounted to nearly 1.4x10(-5)% of the dose. No accumulation of the adducts was observed. Due to rapid depurination from the DNA, the excretion of both N3 adenine and N7 guanine adducts ceased shortly after finishing the exposure. Both N3 adenine and N7 guanine adducts may be used as non-invasive biomarkers of effective dose reflecting only a short time exposure to styrene.
在接触苯乙烯蒸气的小鼠尿液中发现了新的尿腺嘌呤加合物，即3-(2-羟基-1-苯乙基)腺嘌呤（N3αA）和3-(2-羟基-2-苯乙基)腺嘌呤（N3βA）。通过HPLC-ESI-MS(2)对这些苯乙烯7,8-氧化物衍生的腺嘌呤加合物以及先前鉴定出的鸟嘌呤加合物7-(2-羟基-1-苯乙基)鸟嘌呤（N7αG）和7-(2-羟基-2-苯乙基)鸟嘌呤（N7βG）进行了定量，并测定了连续10天（每天6小时）重复接触600mg/m(3)或1200mg/m(3)苯乙烯期间及之后的排泄情况。排泄呈剂量依赖性。排泄的总N3腺嘌呤加合物（N3αA+N3βA）相当于吸收剂量的近0.8×10(-5)%，而尿N7鸟嘌呤加合物（N7αG+N7βG）相当于剂量的近1.4×10(-5)%。未观察到加合物的积累。由于DNA的快速脱嘌呤作用，接触结束后不久，N3腺嘌呤和N7鸟嘌呤加合物的排泄就停止了。N3腺嘌呤和N7鸟嘌呤加合物均可作为有效剂量的非侵入性生物标志物，仅反映短时间接触苯乙烯的情况。
