[Effect of hydroquinone on expression of topoisomerase enzyme IIα in human bone marrow mononuclear cells].
OBJECTIVE
To investigate the effects of hydroquinone (HQ) on expression of topoisomerase IIα (TOPOIIα) in human bone marrow mononuclear cells, and to explore the role and possible regulatory mechanism of TOPOIIα involved in toxicity of HQ to hematopoietic cells.


METHODS
After human bone marrow mononuclear cells were exposed to 50 µmol/L HQ (used the cells which were exposed to sterile distilled water as control); the activity of TOPOII was measured by TOPOII assay kit; the expression levels of TOPOIIα mRNA and protein were detected by RT-PCR technique and Western blotting method respectively; the chromatin immunoprecipitation (ChIP) assay was carried out to study the possible mechanism of TOPOIIα expression changes.


RESULTS
(1) The activity of TOPOII was inhibited obviously; the protein and mRNA expression of TOPOIIα were 0.017 ± 0.029 and 0.610 ± 0.128, significantly lower than that in the control with the significant difference (P < 0.01) after treated with HQ for 10 h; (2) The decreased content of TOPOIIα was associated with descended level of histone H4 acetylation than in the control, from 1.198 ± 0.056 to 0.324 ± 0.229, with the significant difference (P < 0.01), without accompanied descended level of histone H3 acetylation, from 1.253 ± 0.045 to 1.177 ± 0.025 (P > 0.05); (3) TOPOIIα mRNA expression decreased gradually after HQ processing, and the chemical modification (histone H4 acetylation) of TOPOIIα promoter happened prior to the mRNA expression.


CONCLUSIONS
HQ could repress the expression of TOPOIIα in human bone marrow mononuclear cells; the change of histone chemical modification plays an important role in the benzene's hematopoietic toxicity.
Department of Hematology, Afficiated One of Wenzhou Medical College, Wenzhou 325000, China.
Yi-fen
YF
Shi
Kang
K
Yu
Yi
Y
Chen
Xing-zhou
XZ
Ren
Lai-xi
LX
Bi
Hong-lan
HL
Qian
D000107:Acetylation; D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D008297:Male; D055815:Young Adult
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D006657:Histones; D006873:Hydroquinones; D004250:DNA Topoisomerases, Type II; C031927:hydroquinone