Induction of centrosome amplification by formaldehyde, but not hydroquinone, in human lymphoblastoid TK6 cells

Abstract

Benzene and formaldehyde (FA) are important industrial chemicals and environmental pollutants that cause leukemia by inducing DNA damage and chromosome aberrations in hematopoietic stem cells (HSC), the target cells for leukemia. Our previous studies showed that workers exposed to benzene and FA exhibit increased levels of aneuploidy in their blood cells. As centrosome amplification is a common phenomenon in human cancers, including leukemia, and is associated with aneuploidy in carcinogenesis, we hypothesized that benzene and FA would induce centrosome amplification in vitro. We treated human lymphoblastoid TK6 cells with a range of concentrations of hydroquinone (HQ, a benzene metabolite) or FA for 24 h, allowed the cells to recover in fresh medium for 24 h, and examined centrosome amplification; chromosomal gain, loss, and breakage; and cytotoxicity. We included melphalan and etoposide, chemotherapeutic drugs that cause therapy-related acute myeloid leukemia and that have been shown to induce centrosome amplification as well as chromosomal aneuploidy and breakage, as positive controls. Melphalan and etoposide induced centrosome amplification and chromosome gain and breakage in a dose-dependent manner, at cytotoxic concentrations. HQ, though cytotoxic, did not induce centrosome amplification or any chromosomal aberration. FA-induced centrosome amplification and cytotoxicity, but did not induce chromosomal aberrations. Our data suggest, for the first time, that centrosome amplification is a potential mechanism underlying FA-induced leukemogenesis, but not benzene-induced leukemogenesis, as mediated through HQ. Future studies are needed to delineate the mechanisms of centrosome amplification and its association with DNA damage, chromosomal aneuploidy and carcinogenesis, following exposure to FA.

Impact of chronic benzene poisoning on aberrant mitochondrial DNA methylation: A prospective observational study

“…A number of biochemical changes are induced by benzene exposure, including changes in histone acetylation and DNA methylation (12). Previously, some studies reported that altered global DNA methylation and endoreduplication were potential mechanisms of aneuploidy induction by the benzene metabolite hydroquinone (HQ) in TK6 cells (13). Signal net analysis of differential methylation genes associated with CBP showed that two key hypomethylated STAT3 was identified (14).…”

Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene‐exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation

“…In recent years, the rapidly increasing incidence of leukemia in both adults and children has become a frequently noted topic in discussions of environmental health, especially because the current occupational exposure limit in China is an 8‐hr time‐weighted average (TWA‐8) of 6 mg/m 3 at 20°C and 1 atmosphere of pressure, which is much higher than that in the US (1 ppm, approximately 3.25 mg/m 3 ). In addition, the genetic toxicity induced by very low benzene levels has raised additional concerns (Ji et al, ; Lovreglio et al, ). The prognostic and predictive biomarkers of benzene‐induced cancer development and progression remain important issues.…”