甲醛染毒大鼠 N2-羟甲基-dG 加合物的分子剂量学研究。
Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde.
机构信息
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
出版信息
Chem Res Toxicol. 2011 Feb 18;24(2):159-61. doi: 10.1021/tx1003886. Epub 2010 Dec 14.
Abstract
In this study, both endogenous and exogenous N(2)-hydroxymethyl-dG adducts in nasal DNA of rats exposed to 0.7, 2, 5.8, 9.1, or 15.2 ppm [(13)CD(2)] formaldehyde for 6 h were quantified by a highly sensitive nano-UPLC-MS/MS method. Our data clearly demonstrated that exogenous formaldehyde DNA adducts form in a highly nonlinear fashion, with a 21.7-fold increase in exposure causing a 286-fold increase in exogenous adducts. The ratio of exogenous/endogenous DNA adducts demonstrated that endogenous DNA adducts dominated at low exposures, comprising more than 99%. In contrast, exogenous adducts were not detectable in the bone marrow of rats exposed to 15.2 ppm [(13)CD(2)] formaldehyde.
摘要
本研究采用高灵敏度的纳升超高效液相色谱-串联质谱法，定量分析了经 0.7、2、5.8、9.1 或 15.2ppm[(13)CD2]甲醛暴露 6 小时的大鼠鼻内 DNA 中的内源性和外源性 N(2)-羟甲基-dG 加合物。我们的数据清楚地表明，外源性甲醛 DNA 加合物的形成呈高度非线性，暴露量增加 21.7 倍导致外源性加合物增加 286 倍。外源性/内源性 DNA 加合物的比例表明，在低暴露水平下，内源性 DNA 加合物占主导地位，超过 99%。相比之下，在暴露于 15.2ppm[(13)CD2]甲醛的大鼠骨髓中未检测到外源性加合物。
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