Zhang L, Rothman N, Wang Y, Hayes R B, Li G, Dosemeci M, Yin S, Kolachana P, Titenko-Holland N, Smith M T
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720-7360, USA.
Carcinogenesis. 1998 Nov;19(11):1955-61. doi: 10.1093/carcin/19.11.1955.
Two of the most common cytogenetic changes in therapy- and chemical-related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.
治疗相关和化学相关白血病中最常见的两种细胞遗传学改变是5号和7号染色体的缺失以及长臂(q)缺失。在接触潜在白血病原的个体淋巴细胞中检测到这些畸变,可作为白血病风险增加的有用生物标志物。我们使用了一种新型荧光原位杂交(FISH)方法,来确定1号、5号和7号染色体的特定畸变在接触苯的工人血细胞中是否以更高的频率出现。对43名接触不同浓度苯(中位数为31 ppm,8小时时间加权平均值)的健康工人和44名来自上海的未接触对照组进行了研究。全血培养72小时后收获中期分裂相。苯暴露与5号和7号染色体单体率增加有关,但与1号染色体单体率无关(分别为P < 0.001、P < 0.0001和P = 0.94),并且与所有三条染色体的三体和四体频率增加有关。5号和7号染色体长臂缺失在接触苯的工人中呈剂量依赖性增加(P = 0.014和P < 0.0001),最高可达3.5倍。这些结果表明,通过FISH可以在接触苯的健康工人外周血中检测到5号和7号染色体的白血病特异性改变。我们认为,5号和7号染色体的畸变可能是苯暴露早期生物学效应的有用生物标志物。