Aberrant DNA Methylation of Two Tumor Suppressor Genes, p14ARF and p15INK4b , after Chronic Occupational Exposure to Low Level of Benzene

Jamebozorgi, Iraj; Majidizadeh, Tayebeh; Pouryagoub, Gholamreza; Mahjoubi, Frouzandeh

doi:10.15171/ijoem.2018.1317

Cited by 21 publications

(10 citation statements)

References 22 publications

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“…Jamebozorgi et al evaluated whether chronic work-related exposure to a small amount of benzene is correlated with the methylation of the p14ARF and p15INK4b promoter CpG islands [ 147 ]. Total DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14ARF and p15INK4b , were performed employing the DNA derived from 40 petrochemical employers subjected to ambient benzene concentrations of <1 ppm, and 31 office employers not subjected to benzene.…”

Section: Epigenetics Hematological Neoplasms and Benzenementioning

confidence: 99%

“…Total DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14ARF and p15INK4b , were performed employing the DNA derived from 40 petrochemical employers subjected to ambient benzene concentrations of <1 ppm, and 31 office employers not subjected to benzene. A rise in total DNA methylation of 5% in p14ARF and 28% in p15INK4b genes was demonstrated in the exposed subjects, while no augmented methylation in the considered genes was detected in the unexposed controls [ 147 ].…”

Section: Epigenetics Hematological Neoplasms and Benzenementioning

confidence: 99%

“…As reported above, exposure to benzene can act on p14 and p15 [ 147 ]. Deactivation of p14ARF would cause degradation of the p53 protein, a possible objective for methylation in tumor [ 153 ].…”

Section: Epigenetics Hematological Neoplasms and Benzenementioning

confidence: 99%

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Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Spatari

Allegra

Carrieri

et al. 2021

Cancers

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Benzene carcinogenic ability has been reported, and chronic exposure to benzene can be one of the risk elements for solid cancers and hematological neoplasms. Benzene is acknowledged as a myelotoxin, and it is able to augment the risk for the onset of acute myeloid leukemia, myelodysplastic syndromes, aplastic anemia, and lymphomas. Possible mechanisms of benzene initiation of hematological tumors have been identified, as a genotoxic effect, an action on oxidative stress and inflammation and the provocation of immunosuppression. However, it is becoming evident that genetic alterations and the other causes are insufficient to fully justify several phenomena that influence the onset of hematologic malignancies. Acquired epigenetic alterations may participate with benzene leukemogenesis, as benzene may affect nuclear receptors, and provoke post-translational alterations at the protein level, thereby touching the function of regulatory proteins, comprising oncoproteins and tumor suppressor proteins. DNA hypomethylation correlates with stimulation of oncogenes, while the hypermethylation of CpG islands in promoter regions of specific tumor suppressor genes inhibits their transcription and stimulates the onset of tumors. The discovery of the systems of epigenetic induction of benzene-caused hematological tumors has allowed the possibility to operate with pharmacological interventions able of stopping or overturning the negative effects of benzene.

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Section: Epigenetics Hematological Neoplasms and Benzenementioning

confidence: 99%

Section: Epigenetics Hematological Neoplasms and Benzenementioning

confidence: 99%

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Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Spatari

Allegra

Carrieri

et al. 2021

Cancers

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“…Moreover, smoking deregulates PIWI-interacting RNAs (piRNAs) [33] and miRNAs [34] in HNSCCs. Alcohol intake [35], and smoking was associated with distinct DNA-methylation changes [10], [36], [37], [38], [39], [40]. Of note, the methylation profile is also different between HPV-positive and negative groups in HNSCC [10].…”

Section: Discussionmentioning

confidence: 93%

Genome-Wide Analysis of Head and Neck Squamous Cell Carcinomas Reveals HPV, TP53, Smoking and Alcohol-Related Allele-Based Acquired Uniparental Disomy Genomic Alterations

2019

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Smoking and alcohol intake are major risk factors in head and neck squamous cell carcinomas (HNSCCs). Although the link between TP53 mutation and smoking has been well established, very little is known about the link between acquired uniparental disomy (aUPD) and smoking and/or alcohol consumption or other clinical characteristics. We used TCGA genomic data to investigate whether smoking, alcohol intake, clinical and demographic variables, HPV status and TP53 mutation are associated with aUPD at specific chromosomal regions. In multivariate analysis, we found association between aUPD regions and risk factors and clinical variables of disease. aUPD regions on chromosome 4q, 5q, 9p, 9q, 13q, 17p and CDKN2A occurred significantly more often in patients with TP53-mutated HNSCC than in those with wild-type HNSCC, while aUPD regions on chromosome 9p and at CDKN2A were significantly more frequent in females than in males. Besides, aUPD occurred more frequent in HPV-positive than in HPV-negative samples with all HNSCC and larynx cancers on chromosome 9q 15q and 17p. Moreover, aUPD on CDKN2A region occurred more often in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers, while aUPD region on chromosome 5q occurred less in alcohol drinkers than nondrinkers in patients with all HNSCC and oral cavity cancers. Similarly, aUPD region on chromosome 5q occurred less in smokers than nonsmokers in patients with all HNSCC and oral cavity cancers. In conclusion, aUPD regions are not random, and certain regions are associated with risk factors for disease, and with TP53 mutation status.

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“…Increasing evidence indicates that epigenetics, such as DNA methylation, acetylation, glycosylation and phosphorylation, play an important role in the occurrence and development of many diseases and regulate gene expression ( Abdel-Hafiz and Horwitz, 2015 ; Wu, et al, 2020 ). Among them, DNA methylation refers to the methyl group in S-adenosylmethionine is transferred to cytosine by DNA methyltransferase (DNMT) to form 5-methylcytosine, which is methylated ( Guarrera, et al, 2019 ; Jamebozorgi, et al, 2018 ). DNA methylation in humans and mammals is mainly associated with CpG dinucleotides, and hypermethylation of CpG islands in the promoter region can inhibit gene expression.…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice

Yong-peng

Xu-dong

et al. 2021

Front. Bioeng. Biotechnol.

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Background: Accumulating evidence has implicated DNA methylation in the progression of atherosclerosis (AS). Rnase6 has been reported to be upregulated in AS development, but the specific regulatory mechanism remains unclear.Material/Methods: Peripheral blood and sclerotic plaque tissues from 25 AS patients were collected to detect Rnase6 expression. Methylation-specific polymerase chain reaction (MSP) was used to detected Rnase6 methylation levels in the peripheral blood of AS patients. Rnase6 expression was knocked down or DNA methyltransferase 1 (DNMT1) was overexpressed in OX-LDL-treated mouse aortic smooth muscle cells (MOVAS), and cell proliferation, migration, ROS content, and inflammatory factor secretion levels were detected. 740 Y-P, a PI3K specific agonist, was introduced to verify the effect of Rnase6 promoter hypomethylation on the PI3K/Akt signaling pathway. We knocked down Rnase6 expression in ApoE−/− mice fed with a high-fat diet to examine Rnase6 promoter methylation levels. Plaque areas and inflammatory factor secretion were examined in AS mice overexpressing DNMT1.Results: Rnase6 expression was upregulated in the peripheral blood and plaque tissues of AS patients, accompanied by decreased methylation levels of the Rnase6 promoter. Interfering with Rnase6 expression or overexpressing DNMT1 in OX-LDL stimulated MOVAS inhibited cell proliferation and migration, decreased ROS content and inflammatory factor secretion, and inhibited PI3K pathway protein expression. Rnase6 expression was decreased in the peripheral blood and plaque tissues of si-Rnase6-injected mice, and Rnase6 promoter methylation was increased. Mice overexpressing DNMT1 showed less plaque areas in the aortic root and lower secretion levels of inflammatory factors.Conclusion: Hypomethylation of the promoter of Rnase6 enhanced the proliferation and migration of OX-LDL treated MOVAS, upregulated ROS content and inflammatory factor secretion levels in the cells, and activated the PI3K/Akt signaling pathway.

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Aberrant DNA Methylation of Two Tumor Suppressor Genes, p14ARF and p15INK4b , after Chronic Occupational Exposure to Low Level of Benzene

Abstract: Chronic occupational exposure to lower than the permissible exposure limit of benzene may still result in DNA methylation of tumor suppressor genes that may ultimately lead to development of cancer.

Cited by 21 publications

References 22 publications

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Epigenetic Effects of Benzene in Hematologic Neoplasms: The Altered Gene Expression

Genome-Wide Analysis of Head and Neck Squamous Cell Carcinomas Reveals HPV, TP53, Smoking and Alcohol-Related Allele-Based Acquired Uniparental Disomy Genomic Alterations

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice

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