Limits...
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.

Show MeSH

Related in: MedlinePlus

White blood cell (WBC) count and number of CFU-GM colonies in unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in WBC cell or CGU-GM colony counts with benzene level, and differences in cell or colony count by benzene exposure category, were tested by negative binomial regression (CFU-GM) and linear regression (WBC). 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<0.001, and **** p<0.0001. WBC and CFU-GM colony counts were significantly lowered in the ≥10 ppm exposed group of workers and with increasing benzene exposure.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3472034&req=5

Figure 3: White blood cell (WBC) count and number of CFU-GM colonies in unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in WBC cell or CGU-GM colony counts with benzene level, and differences in cell or colony count by benzene exposure category, were tested by negative binomial regression (CFU-GM) and linear regression (WBC). 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<0.001, and **** p<0.0001. WBC and CFU-GM colony counts were significantly lowered in the ≥10 ppm exposed group of workers and with increasing benzene exposure.

Mentions: WBC and CFU-GM colony counts were significantly lowered in the group of workers exposed to ≥10 ppm (p<0.01), but not in the group exposed to <10 ppm, relative to controls (Figure 3). However, the inverse trends for both WBC and CFU-GM colony counts with increasing exposure were highly significant (ptrends=0.0027 and 0.0007, respectively). In both the <10 ppm and ≥10 ppm exposure groups, the proportional increase in monosomy 7 in the myeloid progenitor cells relative to controls (20% and 48%, respectively) was greater than the corresponding decreases in both WBC (5% and 25%) and CFU-GM (5% and 30 %) counts. Similarly, in both the <10 ppm and ≥10 ppm exposure groups, the proportional increases in CFU-GM monosomy 8 levels relative to controls (28% and 32%, respectively) were greater than the corresponding decreases in WBC (5% and 25%). The increase in CFU-GM monosomy 8 level (28%) was also proportionally greater than the decrease in CFU-GM (5%) count at <10 ppm benzene.


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)

White blood cell (WBC) count and number of CFU-GM colonies in unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in WBC cell or CGU-GM colony counts with benzene level, and differences in cell or colony count by benzene exposure category, were tested by negative binomial regression (CFU-GM) and linear regression (WBC). 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<0.001, and **** p<0.0001. WBC and CFU-GM colony counts were significantly lowered in the ≥10 ppm exposed group of workers and with increasing benzene exposure.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: White blood cell (WBC) count and number of CFU-GM colonies in unexposed controls and subjects exposed to <10 ppm and ≥10 ppm benzeneTrends in WBC cell or CGU-GM colony counts with benzene level, and differences in cell or colony count by benzene exposure category, were tested by negative binomial regression (CFU-GM) and linear regression (WBC). 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<0.001, and **** p<0.0001. WBC and CFU-GM colony counts were significantly lowered in the ≥10 ppm exposed group of workers and with increasing benzene exposure.
Mentions: WBC and CFU-GM colony counts were significantly lowered in the group of workers exposed to ≥10 ppm (p<0.01), but not in the group exposed to <10 ppm, relative to controls (Figure 3). However, the inverse trends for both WBC and CFU-GM colony counts with increasing exposure were highly significant (ptrends=0.0027 and 0.0007, respectively). In both the <10 ppm and ≥10 ppm exposure groups, the proportional increase in monosomy 7 in the myeloid progenitor cells relative to controls (20% and 48%, respectively) was greater than the corresponding decreases in both WBC (5% and 25%) and CFU-GM (5% and 30 %) counts. Similarly, in both the <10 ppm and ≥10 ppm exposure groups, the proportional increases in CFU-GM monosomy 8 levels relative to controls (28% and 32%, respectively) were greater than the corresponding decreases in WBC (5% and 25%). The increase in CFU-GM monosomy 8 level (28%) was also proportionally greater than the decrease in CFU-GM (5%) count at <10 ppm benzene.

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