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.