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Changes in miR-222 expression, DNA repair capacity, and MDM2-p53 axis in association with low-dose benzene genotoxicity and hematotoxicity.
Wang, Tong-Shuai; Tian, Wei; Fang, Yan; Guo, Kong-Rong; Li, An-Qi; Sun, Yuan; Wu, Han-Tian; Zheng, Guo-Qiao; Feng, Nan-Nan; Xing, Cai-Hong; Au, William W; Sun, Dao-Yuan; Xia, Zhao-Lin.
Afiliación
  • Wang TS; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Tian W; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Fang Y; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Guo KR; Department of Occupational Disease, Shanghai Pulmonary Hospital/Shanghai Hospital for Occupational Disease Prevention and Treatment, Shanghai 200082, China.
  • Li AQ; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Sun Y; Shanghai Institute of Occupational Disease for Chemical Industry (Shanghai Institute of Occupational Safety & Health), Shanghai, 200040, China.
  • Wu HT; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Zheng GQ; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
  • Feng NN; School of Public Health, School of Medicine of Shanghai Jiaotong University, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai 200050, China.
  • Xing CH; Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100032, China.
  • Au WW; University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania; Shantou University Medical College, Shantou 515000, China.
  • Sun DY; Department of Occupational Disease, Shanghai Pulmonary Hospital/Shanghai Hospital for Occupational Disease Prevention and Treatment, Shanghai 200082, China. Electronic address: dysun@163.com.
  • Xia ZL; Department of Occupation Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China. Electronic address: zlxia@shmu.edu.cn.
Sci Total Environ ; 765: 142740, 2021 Apr 15.
Article en En | MEDLINE | ID: mdl-33071125
Mechanisms for hematotoxicity and health effects from exposure to low doses of benzene (BZ) remain to be identified. To address the information gap, our investigation was focused onto using appropriate populations and cell cultures to investigate novel BZ-induced effects such as disruption of DNA repair capacity (DRC). From our study, abnormal miRNAs were identified and validated using lymphocytes from 56 BZ-poisoned workers and 53 controls. In addition, 173 current BZ-exposed workers and 58 controls were investigated for key miRNA expression using RT-PCR and for cellular DRC using a challenge assay. Subsequently, the observed activities in lymphocytes were verified using human HL-60 (p53 null) and TK6 (p53 wild-type) cells via 1,4-benzoquinone (1,4-BQ) treatment and miR-222 interferences. The targeting of MDM2 by miR-222 was validated using a luciferase reporter. Our results indicate induction of genotoxicity in lymphocytes from workers with low exposure doses to BZ. In addition, miR-222 expression was up-regulated among both BZ-poisoned and BZ-exposed workers together with inverse association with DRC. Our in vitro validation studies using both cell lines indicate that 1,4-BQ exposure increased expression of miR-222 and Comet tail length but decreased DRC. Loss of miR-222 reduced DNA damage, but induced S-phase arrest and apoptosis. However, silencing of MDM2 failed to activate p53 in TK6 cells. In conclusion, our in vivo observations were confirmed by in vitro studies showing that BZ/1,4-BQ exposures caused genotoxicity and high expression of miR-222 which obstructed expression of the MDM2-p53 axis that led to failed activation of p53, abnormal DRC and serious biological consequences.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benceno / MicroARNs Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Total Environ Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benceno / MicroARNs Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Total Environ Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos