Czene Kamila, Osterman-Golkar Siv, Yun Xiao, Li Gang, Zhao Fulin, Pérez Hermes Licea, Li Ming, Natarajan A T, Segerbäck Dan
Department of Biosciences, Karolinska Institute, Novum, S-141 57 Huddinge, Sweden.
Cancer Epidemiol Biomarkers Prev. 2002 Mar;11(3):315-8.
Propylene oxide (PO), a simple alkylating agent used in the chemical industry, is weakly genotoxic and induces nasal cavity tumors in rodents on inhalation at high air concentrations. DNA adducts, hemoglobin adducts, and sister chromatid exchanges (SCE) were analyzed as biomarkers of exposure in a group of eight PO-exposed workers and eight nonexposed subjects. 1-2-Hydroxypropyladenine (1-HP-adenine) in DNA of WBCs was analyzed using a hypersensitive (32)P-postlabeling assay. HP-valine in hemoglobin was measured using gas chromatography/tandem mass spectrometry. Air measurements indicated PO levels in the range of 1-7 ppm. All three biomarkers showed significantly increased levels in the exposed workers. 1-HP-adenine was recorded in seven of the exposed workers (mean 0.66 mol/10(9) mol nucleotides) but was not detected in any of the control subjects. HP-valine was found in all subjects (means of 2.7 and 0.006 pmol/mg globin in exposed workers and controls, respectively). The average frequencies of SCE were 3.7/cell in exposed workers and 2.0/cell in controls, respectively. DNA and hemoglobin adducts were correlated (r = 0.887), as well as DNA adducts and SCE (r = 0.792) and hemoglobin adducts and SCE (r = 0.762). The present study is the first demonstrating PO-DNA adducts in human individuals. It is also the first study indicating cytogenetic effects in humans from PO exposure, although confounding effects from other sources cannot be excluded.
环氧丙烷（PO）是一种用于化学工业的简单烷基化剂，具有弱遗传毒性，在高空气浓度吸入时会诱发啮齿动物鼻腔肿瘤。对一组8名接触PO的工人和8名未接触者进行了分析，将DNA加合物、血红蛋白加合物和姐妹染色单体交换（SCE）作为接触生物标志物。使用超灵敏的（32）P后标记分析法分析白细胞DNA中的1-2-羟丙基腺嘌呤（1-HP-腺嘌呤）。使用气相色谱/串联质谱法测量血红蛋白中的HP-缬氨酸。空气测量表明PO水平在1-7 ppm范围内。所有三种生物标志物在接触工人中均显示出显著升高的水平。在7名接触工人中检测到1-HP-腺嘌呤（平均0.66 mol/10（9）mol核苷酸），但在任何对照受试者中均未检测到。在所有受试者中均发现了HP-缬氨酸（接触工人和对照中血红蛋白的平均值分别为2.7和0.006 pmol/mg）。接触工人和对照中SCE的平均频率分别为3.7/细胞和2.0/细胞。DNA和血红蛋白加合物相关（r = 0.887），DNA加合物和SCE相关（r = 0.792），血红蛋白加合物和SCE相关（r = 0.762）。本研究首次在人类个体中证明了PO-DNA加合物。这也是第一项表明PO暴露对人类有细胞遗传学影响的研究，尽管不能排除其他来源的混杂影响。
