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Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.

Zhang L, Lan Q, Ji Z, Li G, Shen M, Vermeulen R, Guo W, Hubbard AE, McHale CM, Rappaport SM, Hayes RB, Linet MS, Yin S, Smith MT, Rothman N - Leukemia (2012)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: School of Public Health, Division of Environmental Health Sciences, University of California, Berkeley, CA, USA.

ABSTRACT
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.

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Monosomy 7 and 8 in CFU-GM cells of unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in chromosomal monosomy rates with benzene exposure and differences in monosomy rates by benzene exposure category (i.e., unexposed controls vs. workers exposed to <10 ppm and ≥10 ppm benzene) were tested by fitting appropriate negative binomial regression models. Models were adjusted for age and sex, and additionally for smoking, alcohol, recent infections and BMI if significant (Table 1). Significant ptrend values are shown. p values are indicated as * p<0.05; ** p<0.01. Levels of monosomy 7 and 8 in CFU-GM were significantly increased at <10 ppm and ≥10 ppm benzene and with increasing benzene exposure
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Figure 1: Monosomy 7 and 8 in CFU-GM cells of unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in chromosomal monosomy rates with benzene exposure and differences in monosomy rates by benzene exposure category (i.e., unexposed controls vs. workers exposed to <10 ppm and ≥10 ppm benzene) were tested by fitting appropriate negative binomial regression models. Models were adjusted for age and sex, and additionally for smoking, alcohol, recent infections and BMI if significant (Table 1). Significant ptrend values are shown. p values are indicated as * p<0.05; ** p<0.01. Levels of monosomy 7 and 8 in CFU-GM were significantly increased at <10 ppm and ≥10 ppm benzene and with increasing benzene exposure

Mentions: The benzene exposed subjects were divided into two exposure groups, below 10 ppm (n=18) and at or above 10 ppm (n=10), in order to evaluate dose-response effects on monosomies 7 and 8. At <10 ppm benzene, levels of monosomy 7 and 8 in CFU-GM were significantly increased by 20% (p=0.0419) and 28% (p=0.0056), respectively, compared with controls. At ≥10 ppm, levels of monosomy 7 and 8 in CFU-GM were significantly increased to a greater degree, by 48% (p=0.0045) and 32% (p=0.0354), respectively, compared with controls. The exposure-response trends in monosomy 7 and 8 with increasing exposure were highly significant (ptrend=0.0033 and 0.0057, respectively), Figure 1.


Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.

Zhang L, Lan Q, Ji Z, Li G, Shen M, Vermeulen R, Guo W, Hubbard AE, McHale CM, Rappaport SM, Hayes RB, Linet MS, Yin S, Smith MT, Rothman N - Leukemia (2012)

Monosomy 7 and 8 in CFU-GM cells of unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in chromosomal monosomy rates with benzene exposure and differences in monosomy rates by benzene exposure category (i.e., unexposed controls vs. workers exposed to <10 ppm and ≥10 ppm benzene) were tested by fitting appropriate negative binomial regression models. Models were adjusted for age and sex, and additionally for smoking, alcohol, recent infections and BMI if significant (Table 1). Significant ptrend values are shown. p values are indicated as * p<0.05; ** p<0.01. Levels of monosomy 7 and 8 in CFU-GM were significantly increased at <10 ppm and ≥10 ppm benzene and with increasing benzene exposure
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472034&req=5

Figure 1: Monosomy 7 and 8 in CFU-GM cells of unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in chromosomal monosomy rates with benzene exposure and differences in monosomy rates by benzene exposure category (i.e., unexposed controls vs. workers exposed to <10 ppm and ≥10 ppm benzene) were tested by fitting appropriate negative binomial regression models. Models were adjusted for age and sex, and additionally for smoking, alcohol, recent infections and BMI if significant (Table 1). Significant ptrend values are shown. p values are indicated as * p<0.05; ** p<0.01. Levels of monosomy 7 and 8 in CFU-GM were significantly increased at <10 ppm and ≥10 ppm benzene and with increasing benzene exposure
Mentions: The benzene exposed subjects were divided into two exposure groups, below 10 ppm (n=18) and at or above 10 ppm (n=10), in order to evaluate dose-response effects on monosomies 7 and 8. At <10 ppm benzene, levels of monosomy 7 and 8 in CFU-GM were significantly increased by 20% (p=0.0419) and 28% (p=0.0056), respectively, compared with controls. At ≥10 ppm, levels of monosomy 7 and 8 in CFU-GM were significantly increased to a greater degree, by 48% (p=0.0045) and 32% (p=0.0354), respectively, compared with controls. The exposure-response trends in monosomy 7 and 8 with increasing exposure were highly significant (ptrend=0.0033 and 0.0057, respectively), Figure 1.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: School of Public Health, Division of Environmental Health Sciences, University of California, Berkeley, CA, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus