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

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.

Fig. 1.

Mean aneuploidy frequencies of all 24 chromosomes in workers exposed to formaldehyde and unexposed controls. Mean unadjusted frequency and standard errors of (A) monosomy, (B) trisomy and (C) tetrasomy for all 24 chromosomes in unexposed controls (n = 23) and exposed workers (n = 29) are shown. P-values indicating significance of the increase relative to controls, which are from models adjusted for covariates shown in Tables 2–4, respectively, are denoted as ****<0.0001, ***<0.001, **<0.01 and *<0.05. X(M) represents X chromosome in males.

Fig. 2.

Mean frequencies of total structural chromosome aberration (SCA) for all 24 chromosomes in workers exposed to formaldehyde and unexposed controls. Mean unadjusted frequency and standard errors of total SCA for all 24 chromosomes in unexposed controls (n = 23) and exposed workers (n = 29) are shown. P-values are from models adjusted for covariates shown in table 5. The P-value indicating significance of the increase relative to controls is denoted as *<0.05. X(M) represents X chromosome in males.