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

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 to 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 ppm (20%, p=0.0419 and 28%, p=0.0056, respectively) and ≥10 ppm (48%, p=0.0045 and 32%, p=0.0354) benzene, compared with controls, and significant exposure-response trends were detected (ptrend=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent fashion in the blood progenitor cells of workers exposed to benzene and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.

Benzene poisoning, clinical and blood abnormalities in two Brazilian female gas station attendants: two case reports

“…However, benzene is considered the main carcinogenic agent (group 1 according to IARC) and studies associate this compound with acquired cytogenetic alterations [5–7]. Among various forms of benzene-induced genetic alterations, aneuploidy and chromosomal breakage are the most studied [4].…”

“…Among various forms of benzene-induced genetic alterations, aneuploidy and chromosomal breakage are the most studied [4]. Chromosomal aberrations in peripheral blood lymphocytes of chronically benzene-exposed patients were previously documented [5–7]. Zhang et al [5] reported dose-dependent chromosomal aneuploidies (mono- and trisomies) in the peripheral blood lymphocytes of workers exposed to benzene.…”

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

“…Zhang et al (2011) has reported dose-dependent chromosomal aneuploidies (monosomy & trisomy) in the peripheral blood lymphocytes of 47 workers exposed to benzene . In another study published by Zhang et al (2012) an increased monosomy 7 and 8 level was found in 28 benzene-exposed workers in comparison to control subjects . Macron et al…”

Toxicological Risk Assessment for Beginners

“…Recent investigations continue to assess and report the frequent detection of increased chromosomal aberrations among benzene exposed leukemia patients (Paz-y-Mino et al 2008;Kim et al 2010;Zhang et al 2011;Ji and Zhang 2012;Zhang et al 2012). For additional studies and investigations on the cytogenetic effects of benzene, please see Kim et al (2004), Holeckova et al (2004), Zhang et al (2002), Marcon et al (1999), Smith et al (1998), Zhang et al (1996), Ciccone et al (1993), Katz et al (1992), Shannon et al (1992), Cuneo et al (1992), Robertson et al (1991), Garson (1984), Rowley (1983) and Mitelman et al (1981).…”