The DNMT1‐associated lncRNA UCA1 was upregulated in TK6 cells transformed by long‐term exposure to hydroquinone and benzene‐exposed workers via DNA hypomethylation

Author(s):  
Zhijie Pan ◽  
Bohuan Zhong ◽  
Xiaoxuan Ling ◽  
Haiqiao Zhang ◽  
Qiang Tan ◽  
...  
2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Menglong Xiang ◽  
Zhi Wang ◽  
Peng Zou ◽  
Xi Ling ◽  
Guowei Zhang ◽  
...  

Abstract Objectives To explore the role of folate metabolism in 1,3-Butadiene (BD)'s genotoxicity, we conducted a match-up study in BD-exposed workers in China to analyze the associations between the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the chromosomal damage induced by BD exposure, and culture-based experiments in TK-6 cells to examine the global DNA methylation levels and chromosomal damage when exposed both to BD’s genotoxic metabolite, 1,2:3,4-diepoxybutane (DEB), and MTHFR’s direct catalytic product, 5-methyltetrahydrofolate (5-MTHF). Methods Cytokinesis block micronucleus assay (CBMN) was used to examine the chromosomal damage induced by BD or DEB. Poisson regression models were produced to quantify the relationship of chromosomal damage and genetic polymorphisms in the BD-exposed workers. Global DNA methylation levels in TK6 cells were examined using DNA Methylation Quantification Kit. Results We found that BD-exposed workers carrying MTHFR C677T CC (2.00 ± 2.00‰) (FR = 0.36, 95%CI: 0.20–0.67, P < 0.01) or MTHFR C677T CT (2.87 ± 1.98‰) (FR = 0.49, 95%CI: 0.32–0.77, P < 0.01) genotypes had significantly lower nuclear bud (NBUD) frequencies than those carrying genotype MTHFR 677 TT (5.33 ± 2.60‰), respectively. The results in TK6 cells showed that there was a significant increment in frequencies of micronucleus (MN), nucleoplasmic bridge (NPB) and nuclear bud (NBUD) with exposure to DEB at each 5-MTHF dose (ANOVA, P < 0.01). Additionally, there was a significant decrease in frequencies of MN, NPB and NBUD in DEB-exposed cultures with increasing concentration of 5-MTHF (ANOVA, P < 0.05). The levels of global DNA methylation were significantly decreased by DEB treatment in a dose-dependent manner within each 5-MTHF concentration in TK-6 cells (ANOVA, P < 0.01), and were significantly increased by 5-MTHF supplementation within each DEB concentration (ANOVA, P < 0.01). Conclusion We reported that folate metabolism could modify the association between BD exposure and chromosomal damage, and such effect may be partially mediated by DNA hypomethylation, and 5-MTHF supplementation could rescue it.


2016 ◽  
Vol 2016 (1) ◽  
Author(s):  
Corrado Magnani ◽  
Francesco Barone-Adesi* ◽  
Daniela Ferrante ◽  
Laura Ancona ◽  
Antonio Baldassarre ◽  
...  

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Deepesh Poudel ◽  
Maia Avtandilashvili ◽  
Luiz Bertelli ◽  
John A. Klumpp ◽  
Sergei Y. Tolmachev

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 187 ◽  
Author(s):  
Sakuya Yamanouchi ◽  
Jordan Rhone ◽  
Jian-Hua Mao ◽  
Keigi Fujiwara ◽  
Premkumar B. Saganti ◽  
...  

During space travel, humans are continuously exposed to two major environmental stresses, microgravity (μG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, as well as using devices that simulated μG on the ground to investigate gravity effects on cells and organisms, and we have gained insights into how living organisms respond to μG. However, our knowledge on how to assess and manage human health risks in long-term mission to the Moon or Mars is drastically limited. For example, little information is available on how cells respond to simultaneous exposure to space radiation and μG. In this study, we analyzed the frequencies of chromosome aberrations (CA) in cultured human lymphoblastic TK6 cells exposed to X-ray or carbon ion under the simulated μG conditions. A higher frequency of both simple and complex types of CA were observed in cells exposed to radiation and μG simultaneously compared to CA frequency in cells exposed to radiation only. Our study shows that the dose response data on space radiation obtained at the 1G condition could lead to the underestimation of astronauts’ potential risk for health deterioration, including cancer. This study also emphasizes the importance of obtaining data on the molecular and cellular responses to irradiation under μG conditions.


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