Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy
Arsenic is a Class I human carcinogen and is widespread in the environment. Chronic arsenic exposure causes cancer in skin, lung and bladder, as well as in other organs. Paradoxically, arsenic also is a potent chemotherapeutic against acute promyelocytic leukemia and can potentiate the cytotoxic eff...
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2015-09-01
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Online Access: | http://www.mdpi.com/2218-273X/5/4/2184 |
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doaj-653e19af0f3f40618d78e2fa5cc0b0a72020-11-24T23:55:52ZengMDPI AGBiomolecules2218-273X2015-09-01542184219310.3390/biom5042184biom5042184Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and ChemotherapyClarisse S. Muenyi0Mats Ljungman1J. Christopher States2Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USADepartments of Radiation Oncology and Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109-2800, USADepartment of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USAArsenic is a Class I human carcinogen and is widespread in the environment. Chronic arsenic exposure causes cancer in skin, lung and bladder, as well as in other organs. Paradoxically, arsenic also is a potent chemotherapeutic against acute promyelocytic leukemia and can potentiate the cytotoxic effects of DNA damaging chemotherapeutics, such as cisplatin, in vitro. Arsenic has long been implicated in DNA repair inhibition, cell cycle disruption, and ubiquitination dysregulation, all negatively impacting the DNA damage response and potentially contributing to both the carcinogenic and chemotherapeutic potential of arsenic. Recent studies have provided mechanistic insights into how arsenic interferes with these processes including disruption of zinc fingers and suppression of gene expression. This review discusses these effects of arsenic with a view toward understanding the impact on the DNA damage response.http://www.mdpi.com/2218-273X/5/4/2184arsenicDNA repairDNA damage responseubiquitinationXPCMSH2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clarisse S. Muenyi Mats Ljungman J. Christopher States |
spellingShingle |
Clarisse S. Muenyi Mats Ljungman J. Christopher States Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy Biomolecules arsenic DNA repair DNA damage response ubiquitination XPC MSH2 |
author_facet |
Clarisse S. Muenyi Mats Ljungman J. Christopher States |
author_sort |
Clarisse S. Muenyi |
title |
Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy |
title_short |
Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy |
title_full |
Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy |
title_fullStr |
Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy |
title_full_unstemmed |
Arsenic Disruption of DNA Damage Responses—Potential Role in Carcinogenesis and Chemotherapy |
title_sort |
arsenic disruption of dna damage responses—potential role in carcinogenesis and chemotherapy |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2015-09-01 |
description |
Arsenic is a Class I human carcinogen and is widespread in the environment. Chronic arsenic exposure causes cancer in skin, lung and bladder, as well as in other organs. Paradoxically, arsenic also is a potent chemotherapeutic against acute promyelocytic leukemia and can potentiate the cytotoxic effects of DNA damaging chemotherapeutics, such as cisplatin, in vitro. Arsenic has long been implicated in DNA repair inhibition, cell cycle disruption, and ubiquitination dysregulation, all negatively impacting the DNA damage response and potentially contributing to both the carcinogenic and chemotherapeutic potential of arsenic. Recent studies have provided mechanistic insights into how arsenic interferes with these processes including disruption of zinc fingers and suppression of gene expression. This review discusses these effects of arsenic with a view toward understanding the impact on the DNA damage response. |
topic |
arsenic DNA repair DNA damage response ubiquitination XPC MSH2 |
url |
http://www.mdpi.com/2218-273X/5/4/2184 |
work_keys_str_mv |
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1725460799354306560 |