Study on the cytogenetic changes induced by benzene and hydroquinone in human lymphocytes.
Benzene (BN) is a prototypical hematotoxicant, genotoxic carcinogen, and ubiquitous environmental pollutant. Although the molecular mechanisms of BN-induced cytotoxicity and genotoxic damage are poorly understood in humans, previous studies suggested that bioactivated BN metabolites are capable of oxidative stress, cell cycle arrest, apoptosis, and DNA damage. The objective of the current study was to investigate the BN-induced cytogenetic changes and underlying mechanisms based on these hypotheses. Peripheral blood lymphocytes (PBLs) might be the targets for BN-induced cytotoxicity and genotoxicity, and therefore DNA damage responses of PBLs after exposure to different concentrations of BN (0.25, 3.5, 50 μmol/L) or BN metabolite, hydroquinone (HQ; 50, 150, 450 μmol/L) were studied in vitro. Microculture tetrazolium assay, flow cytometry, 2',7'-dichlorodihydrofluorescein-diacetate assay, comet assay, micronuclei assay, and attenuated total reflectance microspectroscope were chosen for this study. Based on the results, we reached the conclusion that different concentrations of BN or HQ significantly inhibited cell growth, induced the arrest of S phase and G2/M phase, and increased late apoptosis in a concentration-dependent manner. Furthermore, evidence was also provided to support the conclusion that BN and HQ induced DNA strand breaks and chromosomal mutations in PBL, which indicated the genotoxicity of BN and HQ. Current evidence has indicated that multiple mechanisms including dysfunction of cell cycle, programmed cell death, oxidative stress, and DNA lesions are likely to contribute to BN-induced cytogenetic changes.
Department of Public Health, School of Basic Medical, Hubei University of Medicine, Shiyan, Hubei, PR China.
D
D
Peng
W
W
Jiaxing
H
H
Chunhui
P
P
Weiyi
W
W
Xiaomin
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001554:Benzene / Q000633:toxicity*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
D004785:Environmental Pollutants; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D001554:Benzene; C031927:hydroquinone