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职业性接触甲醛工人培养循环髓系祖细胞的全染色体非整倍体研究。

Chromosome-wide aneuploidy study of cultured circulating myeloid progenitor cells from workers occupationally exposed to formaldehyde.

机构信息

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute (NIH), Bethesda, MD 20892, USA, Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA, Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht NL-3508, The Netherlands, Department of Occupational Health, Qiaotou Hospital, Dongguan, Guangdong 523323, China and Department of Occupational Health, Dongguan Center for Disease Control and Prevention, Guangdong 523129, China

Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.

出版信息

Carcinogenesis. 2015 Jan;36(1):160-7. doi: 10.1093/carcin/bgu229. Epub 2014 Nov 12.

Abstract

Formaldehyde (FA) is an economically important industrial chemical to which millions of people worldwide are exposed environmentally and occupationally. Recently, the International Agency for Cancer Research concluded that there is sufficient evidence that FA causes leukemia, particularly myeloid leukemia. To evaluate the biological plausibility of this association, we employed a chromosome-wide aneuploidy study approach, which allows the evaluation of aneuploidy and structural chromosome aberrations (SCAs) of all 24 chromosomes simultaneously, to analyze cultured myeloid progenitor cells from 29 workers exposed to relatively high levels of FA and 23 unexposed controls. We found statistically significant increases in the frequencies of monosomy, trisomy, tetrasomy and SCAs of multiple chromosomes in exposed workers compared with controls, with particularly notable effects for monosomy 1 [P = 6.02E-06, incidence rate ratio (IRR) = 2.31], monosomy 5 (P = 9.01E-06; IRR = 2.24), monosomy 7 (P = 1.57E-05; IRR = 2.17), trisomy 5 (P = 1.98E-05; IRR = 3.40) and SCAs of chromosome 5 (P = 0.024; IRR = 4.15). The detection of increased levels of monosomy 7 and SCAs of chromosome 5 is particularly relevant as they are frequently observed in acute myeloid leukemia. Our findings provide further evidence that leukemia-related cytogenetic changes can occur in the circulating myeloid progenitor cells of healthy workers exposed to FA, which may be a potential mechanism underlying FA-induced leukemogenesis.

摘要

甲醛(FA)是一种具有重要经济意义的工业化学品,全世界数以百万计的人在环境中和工作中接触到 FA。最近,国际癌症研究机构得出结论,有足够的证据表明 FA 会导致白血病,特别是髓性白血病。为了评估这种关联的生物学合理性,我们采用了全染色体非整倍体研究方法,该方法可以同时评估所有 24 条染色体的非整倍体和结构染色体异常(SCA),以分析 29 名暴露于相对高水平 FA 的骨髓造血祖细胞和 23 名未暴露对照者的骨髓造血祖细胞。我们发现,与对照组相比,暴露组的单倍体、三倍体、四倍体和多条染色体 SCA 的频率均有统计学意义的增加,其中单倍体 1 尤为显著[P=6.02E-06,发病率比(IRR)=2.31]、单倍体 5(P=9.01E-06;IRR=2.24)、单倍体 7(P=1.57E-05;IRR=2.17)、三倍体 5(P=1.98E-05;IRR=3.40)和 5 号染色体 SCA(P=0.024;IRR=4.15)。单倍体 7 和 5 号染色体 SCA 水平的增加尤其具有重要意义,因为它们经常在急性髓性白血病中观察到。我们的研究结果进一步证明,暴露于 FA 的健康工人的循环髓系造血祖细胞中可能发生与白血病相关的细胞遗传学改变,这可能是 FA 诱导白血病发生的潜在机制。

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