Zhong Weiguang, Que Hee Shane S
Department of Environmental Health Sciences, School of Public Health, University of California at Los Angeles, 650 Charles Young Jr Drive South, 90095-1772, USA.
Mutat Res. 2004 Sep 12;563(1):13-24. doi: 10.1016/j.mrgentox.2004.05.012.
Formaldehyde (FA) is a mutagen that, at high concentrations and long durations, has been reported to cause nasal cancer in rats and in some humans. The level of FA-induced modified DNA in nasal cells should serve as a biomarker of FA exposure and effect. In the present study, a high-performance liquid chromatography (HPLC)-ultraviolet (UV) method at 254 nm was developed and optimized to detect and quantify hydroxymethyldeoxynucleosides after the isolated DNA in exposed human nasal epithelial cells (HNEC) was enzymically digested. Normal and modified deoxynucleosides were successfully resolved from one another and from tissue and enzyme blank interferences. The viability of HNEC exposed to FA in solution for 24 h decreased, and there was a linear dose response between % nonviability and FA dose from 10 to 500 microg/mL. Amounts of 18.0 +/- 1.5 pmol N6-dA and 12.0 +/- 1.2 pmol N2-dG derivatives were determined in a 10 microL injection after 1.4 x 10(7) HNEC (106 microg DNA) were exposed to 500 microg/mL in solution. The respective tissue concentrations in pmol hydroxymethyldeoxynucleoside/mg DNA were 170 +/- 14 and 113 +/- 11. The lower quantifiable limits were about 97 and 88 pmol/mg DNA, respectively. Diffusive exposure of HNEC to air FA up to 100 ppm (v/v) for 24 h did not produce quantifiable hydroxymethylnucleosides. FA-modified deoxynucleosides may be useful biomarkers for FA exposure in biological monitoring samples taken by nasal lavage or brush biopsy.
甲醛（FA）是一种诱变剂，据报道，在高浓度和长时间暴露的情况下，会导致大鼠和部分人类患鼻癌。鼻细胞中FA诱导的DNA修饰水平应作为FA暴露和效应的生物标志物。在本研究中，开发并优化了一种在254 nm波长下的高效液相色谱（HPLC）-紫外（UV）方法，用于检测和定量暴露的人鼻上皮细胞（HNEC）中分离的DNA经酶消化后的羟甲基脱氧核苷。正常和修饰的脱氧核苷成功地与彼此以及组织和酶空白干扰物区分开来。溶液中暴露于FA 24小时的HNEC活力下降，在10至500μg/mL的FA剂量范围内，非活力百分比与FA剂量之间存在线性剂量反应。在1.4×10⁷个HNEC（106μg DNA）暴露于500μg/mL的溶液中后，10μL进样量中测定出18.0±1.5 pmol的N6-dA和12.0±1.2 pmol的N2-dG衍生物。羟甲基脱氧核苷的组织浓度分别为170±14和113±11 pmol/mg DNA。可定量下限分别约为97和88 pmol/mg DNA。HNEC在高达100 ppm（v/v）的空气FA中扩散暴露24小时未产生可定量的羟甲基核苷。FA修饰的脱氧核苷可能是通过鼻腔灌洗或刷检采集的生物监测样本中FA暴露的有用生物标志物。
