Abstract:
:Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded within mtDNA, the mitochondrial proteome comprises over 1500 proteins that are encoded by nuclear genes and translocated to the mitochondria for the purpose of maintaining mitochondrial function. Regulation of mtDNA and mitochondrial proteins by epigenetic changes and post-translational modifications facilitate crosstalk between the nucleus and the mitochondria and ultimately lead to the maintenance of cellular health and homeostasis. DNA methyl transferases have been identified in the mitochondria implicating that methylation occurs within this organelle; however, the extent to which mtDNA is methylated has been debated for many years. Mechanisms of demethylation within this organelle have also been postulated, but the exact mechanisms and their outcomes is still an active area of research. Mitochondrial dysfunction in the form of altered gene expression and ATP production, resulting from epigenetic changes, can lead to various conditions including aging-related neurodegenerative disorders, altered metabolism, changes in circadian rhythm, and cancer. Here, we provide an overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post-translational modifications of nucleoid proteins (as mitochondria lack histones). We also highlight the influence of xenobiotics such as airborne environmental pollutants, contamination from heavy metals, and therapeutic drugs on mtDNA methylation. Environ. Mol. Mutagen., 60:668-682, 2019. © 2019 Wiley Periodicals, Inc.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Sharma N,Pasala MS,Prakash Adoi
10.1002/em.22319subject
Has Abstractpub_date
2019-10-01 00:00:00pages
668-682issue
8eissn
0893-6692issn
1098-2280journal_volume
60pub_type
杂志文章,评审abstract::To evaluate whether blood-based genotoxicity endpoints can provide temporal and dose-response data within the low-dose carcinogenic range that could contribute to carcinogenic mode of action (MoA) assessments, we evaluated the sensitivity of flow cytometry-based micronucleus and Pig-a gene mutation assays at and below...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21846
更新日期:2014-05-01 00:00:00
abstract::A collaborative international trial was conducted to evaluate the reproducibility and transferability of an in vivo mutation assay based on the enumeration of CD59-negative rat erythrocytes, a phenotype that is indicative of Pig-a gene mutation. Fourteen laboratories participated in this study, where anti-CD59-PE, SYT...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20672
更新日期:2011-12-01 00:00:00
abstract::Transgenic rodents are valuable models for investigating the genotoxicity of chemicals in vivo. Here, we report the establishment of a novel transgenic rat for genotoxicity analysis. In this model, about 10 copies of lambdaEG10 DNA carrying the gpt gene of E. coli and the red/gam genes of lambda phage are integrated p...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10152
更新日期:2003-01-01 00:00:00
abstract::Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration,...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2280(1997)29:1<73::aid-em10>3.0
更新日期:1997-01-01 00:00:00
abstract::Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20003
更新日期:2004-01-01 00:00:00
abstract::Nitrous acid (NA) is often presumed to cause base substitutions in organisms with double-stranded DNA as a direct consequence of oxidative deamination of adenine and of cytosine residues. Here we summarize evidence indicating that other mechanisms are involved in the case of NA-induced G/C-->A/T transition mutations. ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850240305
更新日期:1994-01-01 00:00:00
abstract::2,6-Dicyano-4-nitroaniline and 2-cyano-4-nitroaniline (CNNA; 2-amino-5-nitrobenzonitrile) are potent mutagens in the Ames test, even though unsubstituted nitroanilines (NAs) are no more than weak mutagens. These compounds are putative reduction products of many commercial azo dyes, including Disperse Blue 165, Dispers...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22161
更新日期:2018-03-01 00:00:00
abstract::A wild-type strain of herpes simplex virus type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk+) and a tk- mutant strain (HSV-1:PTK3B) were used to study the role of the viral tk in the repair of UV-irradiated HSV-1 in human cells. UV survival of HSV-1:PTK3B was substantially reduced compared with that of HS...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850150104
更新日期:1990-01-01 00:00:00
abstract::Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22127
更新日期:2017-10-01 00:00:00
abstract::Gene therapy has been proposed to have implications in the treatment of cancer. By genetically manipulating the hematopoietic stem cell compartment with genes that confer resistance to chemotherapeutic agents, the dose escalation that is necessary to effectively treat the cancers could potentially be achieved. DNA rep...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/(sici)1098-2280(2000)35:2<71::aid-em1>3.0.
更新日期:2000-01-01 00:00:00
abstract::The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and cytogenetic end points was studied in 15 workers and 11 controls. The exposed group consisted of 8 smokers and 7 nonsmokers, whereas the control group consisted of 7 n...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1031
更新日期:2001-01-01 00:00:00
abstract::This collection of articles was inspired by the long-standing relationship between the Environmental Mutagen Society and Latin American scientists, and by the program for the 39th Environmental Mutagen Society meeting in Puerto Rico in 2008, which included a symposium featuring "South of the border" scientists. This c...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20563
更新日期:2010-10-01 00:00:00
abstract::The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA-sequencing (RNA-seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (≥5 ppm) in a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21801
更新日期:2013-08-01 00:00:00
abstract::Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Amoxicillin (AMO), a drug used in the treatment of infections caused by susceptible bacteria, has been evaluated for its ability to induce genotoxicity in human peripheral blood lymphocytes. The potential genotoxic effects of AMO were investigated in vitro by the sister chromatid exchange (SCE), chromosomal aberration...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20531
更新日期:2010-04-01 00:00:00
abstract::The induction and nature of mutations in the lacI transgene were evaluated in multiple tissues after exposure of adult male B6C3F1 lacI transgenic mice to cyclophosphamide (CP). Mice were given a single i.p. injection of 25 mg CP/kg, 100 mg CP/kg, or vehicle (PBS) and then necropsied 6 weeks after treatment to allow D...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::The genome is programmed by the epigenome. Two of the fundamental components of the epigenome are chromatin structure and covalent modification of the DNA molecule itself by methylation. DNA methylation patterns are sculpted during development and it has been a long held belief that they remain stable after birth in s...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.20357
更新日期:2008-01-01 00:00:00
abstract::Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI...
journal_title:Environmental and molecular mutagenesis
pub_type: 信件
doi:10.1002/em.22260
更新日期:2019-04-01 00:00:00
abstract::A working group of five statisticians experienced in the use of statistical methods in mutagenicity reviewed aspects of the statistical analysis of genotoxicity test procedures. Issues discussed included methods for integrating biological importance and statistical significance, the relationship of the experimental un...
journal_title:Environmental and molecular mutagenesis
pub_type:
doi:
更新日期:2000-01-01 00:00:00
abstract::Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The intera...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22113
更新日期:2018-01-01 00:00:00
abstract::Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman Micro...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,多中心研究
doi:
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Recently, high concentrations of arsenic have been documented in ground waters of Southern Assam, India. Indiscriminate smokeless tobacco consumption is a common practice in this region. Correlation between nutritional status and arsenic and smokeless tobacco-induced health effects has not been taken up in h...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22188
更新日期:2018-06-01 00:00:00
abstract::We evaluated the effects of urban air pollutants on human nasal mucosa over an 8-month period on 102 subjects living in Florence, Tuscany, Italy. A group of subjects living in a city with a lower level of pollution (Sassari, Sardinia, Italy) was also analyzed. Nasal mucosa cells were harvested by brushing, a noninvasi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10188
更新日期:2003-01-01 00:00:00
abstract::As a contribution to the second round of rodent carcinogenesis prediction organised by the U.S. National Institute of Environmental Health Sciences (NIEHS), speculative predictions for 30 chemicals currently under evaluation in U.S. National Toxicology Program (NTP) rodent bioassays are presented. Core chemical data r...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)27:3<237::AID-EM9>3.0
更新日期:1996-01-01 00:00:00
abstract::During the development of cancer a series of specific genetic alterations have to occur in a stepwise fashion to transform a normal somatic cell into a malignant tumor cell. These genetic changes can be roughly divided in two groups: mutations in proto-oncogenes that result in a constantly activated gene product and m...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::Third instar larvae of Drosophila melanogaster transdihybrid for mwh and flr were exposed to varying concentrations of cisplatin by feeding on dry media wetted with aqueous solutions of the test compound. Larval feeding continued until pupation, and surviving transdihybrid adults were collected seven days following co...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850100210
更新日期:1987-01-01 00:00:00
abstract::The objective of our study was to develop a micronucleus (MN) assay for detecting genotoxic damage after inhalation exposure in mouse alveolar Type II and Clara cells, potential target cells for lung carcinogens. Ten male C57BL/6J mice were exposed to ethylene oxide (630 mg/m(3)) for 4 hr via inhalation; 10 unexposed ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20520
更新日期:2010-03-01 00:00:00
abstract::The DNA repair proteins XPD and XRCC1 are involved in the nucleotide and base excision repair of DNA lesions induced by many tobacco and environmental carcinogens. Common variant alleles at the XPD (312Asn, 751Gln) and XRCC1 (399Gln) loci have been identified and associated with increased risk for lung cancer. We ther...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10128
更新日期:2003-01-01 00:00:00
abstract::DNA polymerase κ (Pol κ) is a specialized DNA polymerase involved in translesion DNA synthesis. Although its bypass activities across lesions are well characterized in biochemistry, its cellular protective roles against genotoxic insults are still elusive. To better understand the in vivo protective roles, we have est...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21961
更新日期:2015-10-01 00:00:00
abstract::Noncovalent DNA interactions, e.g., DNA intercalation and DNA groove-binding, have not been well studied relative to covalent interactions largely due to the inability of predicting and detecting such events in intact cells. We have adapted an in vitro bleomycin amplification method for DNA intercalation for use in cu...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.20096
更新日期:2005-03-01 00:00:00