Abstract:
:The human transcriptome is complex, comprising multiple transcript types, mostly in the form of non-coding RNA (ncRNA). The majority of ncRNA is of the long form (lncRNA, ≥ 200 bp), which plays an important role in gene regulation through multiple mechanisms including epigenetics, chromatin modification, control of transcription factor binding, and regulation of alternative splicing. Both mRNA and ncRNA exhibit additional variability in the form of alternative splicing and RNA editing. All aspects of the human transcriptome can potentially be dysregulated by environmental exposures. Next-generation RNA sequencing (RNA-Seq) is the best available methodology to measure this although it has limitations, including experimental bias. The third phase of the MicroArray Quality Control Consortium project (MAQC-III), also called Sequencing Quality Control (SeQC), aims to address these limitations through standardization of experimental and bioinformatic methodologies. A limited number of toxicogenomic studies have been conducted to date using RNA-Seq. This review describes the complexity of the human transcriptome, the application of transcriptomics by RNA-Seq or microarray in molecular epidemiology studies, and limitations of these approaches including the type of cell or tissue analyzed, experimental variation, and confounding. By using good study designs with precise, individual exposure measurements, sufficient power and incorporation of phenotypic anchors, studies in human populations can identify biomarkers of exposure and/or early effect and elucidate mechanisms of action underlying associated diseases, even at low doses. Analysis of datasets at the pathway level can compensate for some of the limitations of RNA-Seq and, as more datasets become available, will increasingly elucidate the exposure-disease continuum.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
McHale CM,Zhang L,Thomas R,Smith MTdoi
10.1002/em.21798subject
Has Abstractpub_date
2013-08-01 00:00:00pages
500-17issue
7eissn
0893-6692issn
1098-2280journal_volume
54pub_type
杂志文章,评审abstract::Occupational exposure to wood dust is associated with the occurrence of nasal cancer. In this study, we investigated micronuclei and nuclear changes (NCs: binucleates, karyorrhexis, karyolysis, and the "broken egg" effect) in exfoliated buccal cells of 20 workers exposed to wood dust and 20 age- and sex-matched contro...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20257
更新日期:2006-12-01 00:00:00
abstract::Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m(-3) DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In t...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20335
更新日期:2007-10-01 00:00:00
abstract::Arsenic is an environmental pollutant capable of causing oxidative stress, disturbance of metabolism, and cancer development. The present study was undertaken to investigate the effects of exposure to sodium arsenite on the glutathione pool, lipid peroxidation, protein carbonyl levels, global DNA methylation, and acti...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20328
更新日期:2007-10-01 00:00:00
abstract::Eleven mutagenic heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]-indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3]indole (Trp-P-2), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C), 2-amino-3-methyl-9H-...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2860120108
更新日期:1988-01-01 00:00:00
abstract::Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22098
更新日期:2017-07-01 00:00:00
abstract::The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy non...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10105
更新日期:2002-01-01 00:00:00
abstract::Coal tar (CT) is a thick black liquid produced as a by-product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in so...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22032
更新日期:2016-08-01 00:00:00
abstract::Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22080
更新日期:2017-04-01 00:00:00
abstract::Chlorinated drinking water contains several chlorohydroxyfuranone (CHF) by-products whose contribution to cancer risk is not presently known. 3,4-Dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), and 3- chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF) were studied for th...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10025
更新日期:2001-01-01 00:00:00
abstract::To protect human and ecosystem health, it is necessary to develop sensitive assays and to identify responsive cells and species (and their life stages). In this study, the relative genotoxicity of two inorganic arsenicals: trivalent sodium arsenite (As(3+)) and pentavalent sodium arsenate (As(5+)), was evaluated in tw...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20027
更新日期:2004-01-01 00:00:00
abstract::A data base consisting of 61 heterocyclic amines formed during food preparation and their des-amino analogs were subjected to structure-activity analysis using the CASE method, a structural activity relational expert system. The program identified the major structural determinants associated with mutagenic activity or...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210114
更新日期:1993-01-01 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::The aim of this research was to study the gaseous and particulate emissions of genotoxic substances during cooking with two types of methane stoves (a new one and an old one). The particulates were sampled both with a cascade impactor air sampler and an impinger with ice trap and analyzed by two bacterial mutagenicity...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 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::The 1960s witnessed detailed studies on the genetic properties of a large number of histidine-requiring mutants of Salmonella typhimurium. The early 1970s saw development of selected strains, the Ames strains, for use in rapid, cheap, sensitive, and manipulable tests of chemicals and chemical mixtures for genotoxic ac...
journal_title:Environmental and molecular mutagenesis
pub_type: 历史文章,杂志文章
doi:10.1002/em.2850140610
更新日期:1989-01-01 00:00:00
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 w...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.22319
更新日期:2019-10-01 00:00:00
abstract::The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3'-untranslated region (3'-U...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22159
更新日期:2018-03-01 00:00:00
abstract::The mitochondrial genome is essential for producing ATP (adenosine 5'-triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.2850250607
更新日期:1995-01-01 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::The placenta is a readily available source of material for molecular epidemiological investigations. As such, DNA damage in this tissue can be indicative of maternal exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs). Previous reports have demonstrated that (32)P-postlabeling (PPL) is...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/1098-2280(2000)36:4<274::aid-em3>3.0.co;2-
更新日期:2000-01-01 00:00:00
abstract::We describe an in vivo mutagenesis model that utilizes reverse mutation and forward mutation at the endogenous Aprt locus. Reverse mutation provides an in situ method for detecting environments or agents that cause point mutations. Forward mutation detects large chromosomal events, including mitotic recombination, chr...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:4<471::AID-EM25>3.
更新日期:1996-01-01 00:00:00
abstract::Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22426
更新日期:2021-01-26 00:00:00
abstract::Riddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria, Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short-term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data availa...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850210310
更新日期:1993-01-01 00:00:00
abstract::N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking wat...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10139
更新日期:2003-01-01 00:00:00
abstract::The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our cells from genomic instability in part by facilitating the efficient repair of DNA double-strand breaks (DSBs). BRCA1 promotes the error-free repair of DSBs through homologous recombination and is also implicated in the regulation of nonh...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21674
更新日期:2012-01-01 00:00:00
abstract::The mutagenic activity of airborne particulate matter collected in Pisa, a small nonindustrial town located in Italy, has been monitored over 1 year using the Ames Salmonella Test. Airborne particulate was collected on fibreglass filters using a Hi-Vol sampler and extracted by sonication and Soxhlet acetone extraction...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850130306
更新日期:1989-01-01 00:00:00
abstract::Clustered damage induced by ionizing radiation--two or more oxidized bases, abasic sites, or strand breaks within a few DNA helical turns--have been postulated to be major lethal and/or mutagenic sites. Although they have recently been shown to be induced in genomic DNAs by ionizing photons and particles, little is kn...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1067
更新日期:2001-01-01 00:00:00
abstract::Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. The SOS global regulatory network consists o...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.22267
更新日期:2019-05-01 00:00:00
abstract::Previously, we determined that elimination of deoxycytidylate (dCMP) deaminase (DCD1) in the yeast Saccharomyces cerevisiae increases the intracellular dCTP:dTTP ratio and reduces the induction of G x C --> A x T transitions in the SUP4-o gene by ethyl methanesulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (M...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::DNA is exposed to endogenous and environmental factors that can form stable lesions. If not repaired, these lesions can lead to transcription/replication blocking or mutagenic bypass. Our previous work has focused on 8,5'-cyclopurine 2'-deoxyribonucleosides, a unique class of oxidatively induced DNA lesions that are s...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20619
更新日期:2011-05-01 00:00:00