Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China

Environ and Mol Mutagen

et al. 2020

To provide a more comprehensive understanding of genotoxic effects from benzene exposure, its effects on induction of mitochondrial DNA copy number (MtDNAcn) and of micronucleus (MN) were investigated using peripheral blood from workers in China. Changes in mtDNAcn and MN were determined using quantitative real‐time polymerase chain reaction (PCR) and cytokinesis‐block micronucleus assays (CBMN), respectively, in 58 control and 174 benzene‐exposed workers in Shanghai, China. Among the exposed workers, relative mtDNAcn increased and then decreased with increasing doses of benzene exposure. Significant and dose‐dependent increase in MN frequencies were observed among the different exposure groups. In addition, the relative mtDNAcn were significantly associated with the MN frequencies in the low‐level exposure group (P = 0.046), but not in the high dose groups. Therefore, the mechanisms for induction of MtDNAcn and MN by benzene may be similar from exposure to low doses but different from high doses. Similar increase of MN frequencies and MtDNAcn may be due to oxidative stress induced by benzene at low concentrations, while higher concentrations may start to initiate the cell death pathway. The pathway may be associated with excessive MtDNAcn which can initiate apoptosis while MN can continue to be induced. However, the differential mechanisms need to be investigated because they may represent different levels of risk for different health consequences. On the other hand, our data indicate that induction of MtDNAcn may be a sensitive genotoxic biomarker for workers with exposure to low dose of benzene. Environ. Mol. Mutagen. 61:355–360, 2020. © 2020 Wiley Periodicals, Inc.

Section: Discussionmentioning

confidence: 99%

“…The CBMN assay was performed according to the standard method (Fenech ; Zhang et al ). For this assay, an additional 1 mL of blood sample from each worker was collected into heparin‐anticoagulation tubes.…”

Section: Methodsmentioning

confidence: 99%

Effects of Micronucleus Frequencies and Mitochondrial DNA Copy Numbers among Benzene‐Exposed Workers in China

Sun

Environ and Mol Mutagen

et al. 2020

“…Previous studies, including ours, indicate that modifications in DNA methylation play an important role in benzene‐induced poisoning and oncogenesis (Smith et al ., 2016; Zhang et al ., 2017). The global DNA methylation and DNA methylation statuses of GSTP1, IL‐6, and CYP2E1, among others, are significantly altered (Jiménezgarza et al ., 2017; Jiménez‐Garza et al ., 2018; Zhang et al ., 2019). However, most of these studies focused on only one or several methylation sites.…”

Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation in CSF3R induces peripheral neutrophil reduction in benzene‐exposure poisoning

Ren

Environ and Mol Mutagen

et al. 2020

Self Cite

Benzene is a global pollutant and has been established to cause leukemia. To better understand the role of DNA methylation in benzene toxicity, peripheral blood mononuclear cells were collected from six benzene-poisoning patients and six matched controls for genome-wide DNA methylation screening by Illumina Infinium Methylation 450 BeadChip. The Gene Chip Human Gene 2.0 ST Array (Affymetrix) was used to analyze global mRNA expression. Compared with the corresponding sites of controls, 442 sites in patients were hypermethylated, corresponding to 253 genes, and 237 sites were hypomethylated, corresponding to 130 genes. The promoter methylation and mRNA expression of CSF3R, CREB5, and F2R were selected for verification by bisulfite sequencing and real-time PCR in a larger data set with 21 cases and 23 controls. The results indicated that promoter methylation of CSF3R (p = .005) and F2R (p = .015) was significantly higher in cases than in controls. Correlation analysis showed that the promoter methylation of CSF3R (p < .001) and F2R (p < .001) was highly correlated with its mRNA expression. In the poisoning cases, neutrophil percentage was significantly different among the high, middle, and low CSF3Rmethylation groups (p = .002). In particular, the neutrophil percentage in the high CSF3R-methylation group (48.10 ± 9.63%) was significantly lower than that in the low CSF3R-methylation group (59.30 ± 6.26%) (p = .012). The correlation coefficient between promoter methylation in CSF3R and the neutrophil percentage was −0.445 (p = .020) in cases and − 0.398 (p = .060) in controls. These results imply that hypermethylation occurs in the CSF3R promoter due to benzene exposure and is significantly associated with a reduction in neutrophils.

“…The 1485 nt long circ_0001946 is derived from cerebellar degeneration-related protein 1 (CDR1). Knockdown of this circRNA was found to increase cisplatin resistance in A549 cells, and the results of a host cell reactivation (HCR) assay and Western blot analysis demonstrated that silencing circ_0001946 activates the nucleotide excision repair (NER) signaling pathway, which increases the ability for DNA damage repair [137], to reduce cisplatin sensitivity in lung cancer.…”

Section: Platinum Drugsmentioning

confidence: 99%

CircRNAs in anticancer drug resistance: recent advances and future potential

Jiang

et al. 2020

Mol Cancer

CircRNAs are a novel class of RNA molecules with a unique closed continuous loop structure. CircRNAs are abundant in eukaryotic cells, have unique stability and tissue specificity, and can play a biological regulatory role at various levels, such as transcriptional and posttranscriptional levels. Numerous studies have indicated that circRNAs serve a crucial purpose in cancer biology. CircRNAs regulate tumor behavioral phenotypes such as proliferation and migration through various molecular mechanisms, such as miRNA sponging, transcriptional regulation, and protein interaction. Recently, several reports have demonstrated that they are also deeply involved in resistance to anticancer drugs, from traditional chemotherapeutic drugs to targeted and immunotherapeutic drugs. This review is the first to summarize the latest research on circRNAs in anticancer drug resistance based on drug classification and to discuss their potential clinical applications.