Chromosome-wide aneuploidy study of cultured circulating myeloid progenitor cells from workers occupationally exposed to formaldehyde.
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.
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 luoping@berkeley.edu qingl@mail.nih.gov.
Qing
Q
Lan
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Martyn T
MT
Smith
Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China.
Xiaojiang
X
Tang
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Weihong
W
Guo
Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht NL-3508, The Netherlands.
Roel
R
Vermeulen
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Zhiying
Z
Ji
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.
Wei
W
Hu
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Alan E
AE
Hubbard
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.
Min
M
Shen
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Cliona M
CM
McHale
Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China.
Chuangyi
C
Qiu
Department of Occupational Health, Qiaotou Hospital, Dongguan, Guangdong 523323, China and.
Songwang
S
Liu
Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht NL-3508, The Netherlands.
Boris
B
Reiss
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.
Laura
L
Beane-Freeman
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.
Aaron
A
Blair
Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China.
Yichen
Y
Ge
Department of Occupational Health, Dongguan Center for Disease Control and Prevention, Guangdong 523129, China.
Jun
J
Xiong
Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China.
Laiyu
L
Li
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA.
Stephen M
SM
Rappaport
Science and Education Department, Guangdong Poisoning Control Center, Guangzhou 510300, China.
Hanlin
H
Huang
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.
Nathaniel
N
Rothman
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA, luoping@berkeley.edu qingl@mail.nih.gov.
Luoping
L
Zhang
D000328:Adult; D000782:Aneuploidy; D016022:Case-Control Studies; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000187:drug effects*; D003430:Cross-Sectional Studies; D004202:Disinfectants / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005557:Formaldehyde / Q000009:adverse effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D023461:Myeloid Progenitor Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects*; D011379:Prognosis
D004202:Disinfectants; D005557:Formaldehyde