Nonrandom aneuploidy of chromosomes 1, 5, 6, 7, 8, 9, 11, 12, and 21 induced by the benzene metabolites hydroquinone and benzenetriol

Abstract

The loss and gain of whole chromosomes (aneuploidy) is common in the development of leukemia and other cancers. In acute myeloid leukemia, the loss (monosomy) of chromosomes 5 and 7 and the gain (trisomy) of chromosome 8 are common clonal chromosomal abnormalities. Here, we have tested the hypothesis that metabolites of the human leukemogen benzene cause a higher rate of gain and loss among the chromosomes involved in leukemogenesis and, as such, are nonrandom and selective in their effects. Human peripheral blood was exposed to two metabolites of benzene, namely, hydroquinone (HQ) and benzenetriol (BT), and the ploidy status of nine different chromosomes (1, 5, 6, 7, 8, 9, 11, 12, and 21) was examined using fluorescence in situ hybridization of metaphase spreads. Poisson regression was used to provide interpretable incidence rate ratios and corresponding P values for all nine chromosomes. Statistically significant differences were found between the sensitivity of the nine chromosomes to gain or loss. Chromosomes 5 and 7 were highly sensitive to loss following HQ and BT exposure, whereas chromosomes 7, 8, and 21 were highly sensitive to gain in comparison to other chromosomes. Significant support for the a priori hypothesis that chromosomes 5 and 7 are more sensitive to loss induced by HQ and BT than the other seven chromosomes was also obtained. These data support the notion that benzene metabolites affect the ploidy status of specific chromosomes more than others and may initiate or promote leukemia induction through these specific effects.

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

“…18). Specific chromosomal aberrations have been observed in both preleukemia and leukemia patients exposed to benzene as well as in otherwise healthy benzene-exposed workers (19). By use of fluorescent in situ hybridization and PCR, Zhang et al found that high occupational benzene exposure increased the frequencies of aberrations in chromosomes 5, 7, 9, 8, and 11, aberrations that are frequently seen in acute myeloid leukemias and in preleukemic myelodysplastic syndrome.…”

Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes

“…However, previous occupational exposure to organic solvents, mainly benzene, has been suggested to increase the risk for AML with +8 as the sole change [47,48]. Further support for an etiologic role of benzene has come from in vitro studies, using interphase fluorescence in situ hybridization (FISH), showing that exposing peripheral blood cells or CD34+ cells from chord blood to metabolites of benzene, e.g., hydroquinone and benzenetriol, results in aneuploidy of chromosome 8 [49][50][51]. This was, however, not confirmed in similar experiments on CD34+ bone marrow cells [52].…”

Trisomy 9 in a Patient with Acute Myelogenous Leukaemia FAB Type M2: A Rare Occurrence

“…Trisomy 8 is very common in acute myeloid leukemia (AML) and portends poor prognosis across all AML subgroups at all ages [2]. Trisomy 9 is rarely reported, when present has intermediate prognosis and has been considered a marker for benzene-related leukemogenesis [3,4]. Both trisomy 8 and 9 are common in systemic mastocytosis and myeloproliferative disorders [5].…”