Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.
Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ≥ 10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.
School of Public Health, Division of Environmental Health Sciences, University of California, Berkeley, CA, USA.
L
L
Zhang
Q
Q
Lan
Z
Z
Ji
G
G
Li
M
M
Shen
R
R
Vermeulen
W
W
Guo
A E
AE
Hubbard
C M
CM
McHale
S M
SM
Rappaport
R B
RB
Hayes
M S
MS
Linet
S
S
Yin
M T
MT
Smith
N
N
Rothman
D000328:Adult; D000782:Aneuploidy; D001554:Benzene / Q000009:adverse effects*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003114:Colony-Forming Units Assay; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D009006:Monosomy; D016273:Occupational Exposure / Q000009:adverse effects*; D011379:Prognosis
D001554:Benzene