Induction of apoptosis in human leukemia cells through the production of reactive oxygen species and activation of HMOX1 and Noxa by benzene, toluene, and o-xylene
- Induction of apoptosis in human leukemia cells through the production of reactive oxygen species and activation of HMOX1 and Noxa by benzene, toluene, and o-xylene
- 샤르마; Youn-Jung Kim; 송미; 류재천
- Benzene; Toluene; o-Xylene; Apoptosis; HMOX1; Noxa
- Issue Date
- VOL 280, NO 3, 109-117
- Whereas benzene (BZ) is a well-known human carcinogen, toluene (TOL) and o-xylene (o-XY) are not;
however, all three compounds are important environmental pollutants. Although BZ, TOL, and o-XY have
been shown to induce apoptosis in vitro, their mechanism of toxicity remains unclear. In this study, we
sought to identify the apoptotic pathway(s) activated by BZ, TOL, and o-XY in human HL-60 promyelocytic
leukemia cells. Cell cycle analysis by propidium iodide (PI) staining and flow cytometric analyses of
Annexin V/PI double-stained cells revealed similar patterns of apoptosis following BZ, TOL, and o-XY exposure.
Though reactive oxygen species (ROS) production contributes significantly to BZ metabolite-induced
apoptotic cell death, we hypothesized that BZ, TOL, and o-XY can themselves trigger ROS production,
leading to the activation of apoptotic signaling. Dose-dependent increases in ROS production and significant
tail moments were observed in HL-60 cells exposed to all three compounds. Real-time RT-PCR
revealed increased HMOX1 and Noxa expression in BZ-, TOL-, and o-XY-treated HL-60 cells, confirming
the results of previous microarray analyses. Similar expression profiles were found in human K562 erythromyeloblastoid
leukemia cells and human U937 leukemic monocyte lymphoma cells. Pretreatment
with the ROS scavenger N-acetyl cysteine decreased the effects of exposure to BZ, TOL, and o-XY. In summary,
this study provides useful insights into the mechanism of BZ-, TOL-, and o-XY-induced apoptosis
in leukemia cells.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.