Abstract:
:Exposure to asbestos fiber is central to mesothelial carcinogenesis. Recent sequencing studies on human and rodent malignant mesothelioma (MM) revealed frequently mutated genes, including CDKN2A, BAP1 and NF2. Crocidolite directly or indirectly catalyses the generation of hydroxyl radicals, which appears to be the major driving force for mesothelial mutations. DNA base modification is an oxidative DNA damage mechanism, where 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most abundant modification both physiologically and pathologically. Multiple distinct mechanisms work together to decrease the genomic level of 8-OHdG through the enzymatic activities of Mutyh, Ogg1 and Mth1. Knockout of one or multiple enzymes is not lethal but increases the incidence of tumors. Here, we used single knockout (KO) mice to test whether the deficiency of these three genes affects the incidence and prognosis of asbestos-induced MM. Intraperitoneal injection of 3 mg crocidolite induced MM at a fraction of 14.8% (4/27) in Mth1 KO, 41.4% (12/29) in Mutyh KO and 24.0% (6/25) in Ogg1 KO mice, whereas 31.7% (20/63) induction was observed in C57BL/6 wild-type (Wt) mice. The lifespan of female Mth1 KO mice was longer than that of female Wt mice (p = 0.0468). Whole genome scanning of MM with array-based comparative genomic hybridization revealed rare genomic alterations compared to MM in rats and humans. These results indicate that neither Mutyh deficiency nor Ogg1 deficiency promotes crocidolite-induced MM in mice, but the sanitizing nucleotide pool with Mth1 is advantageous in crocidolite-induced mesothelial carcinogenesis.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Funahashi S,Okazaki Y,Akatsuka S,Takahashi T,Sakumi K,Nakabeppu Y,Toyokuni Sdoi
10.1080/10715762.2020.1743285subject
Has Abstractpub_date
2020-03-01 00:00:00pages
195-205issue
2-3eissn
1071-5762issn
1029-2470journal_volume
54pub_type
杂志文章abstract::The synproportionation reaction between ferryl leghemoglobin and oxyleghemoglobin does not occur, at least under conditions where this process could be clearly demonstrated with myoglobin and hemoglobin. In contrast, a cross synproportionation can occur between oxyleghemoglobin and ferryl myoglobin or between ferryl l...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769709097848
更新日期:1997-08-01 00:00:00
abstract::Enhanced oxidative stress partly resulting from an over-production of superoxide anion (O(2)(•-)) represents a novel and particular risk factor in chronic kidney disease (CKD) patients. This study was therefore designed to evaluate O(2)(•-) determinants in this population. O(2)(•-) production was evaluated using chemi...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2011.574291
更新日期:2011-06-01 00:00:00
abstract::Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760000301011
更新日期:2000-11-01 00:00:00
abstract::The beneficial effects of hyperoxia have been noted in treatment of several diseases and pathological states. However, the excessive production of ROS under hyperoxic conditions can directly damage cellular macromolecules if the imbalance in antioxidant status exists. Cytochrome P450 (Cyp) 4a14 has an important role i...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715760903390820
更新日期:2010-02-01 00:00:00
abstract::Human serum samples were evaluated for oxidative stress with the d-ROMs test. The ceruloplasmin (CP) and copper contents of the samples was independently measured and compared to those calculated on the basis of the d-ROMs test results for pure CP solutions. The d-ROMs readings did not show any significant correlation...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1136063
更新日期:2016-01-01 00:00:00
abstract::Liposomes composed of soybean phosphatidylcholine were peroxidized using the reagent sodium hypochlorite or the myeloperoxidase-hydrogen peroxide-Cl- system. Linoleic acid hydroperoxide previously prepared from linoleic acid by means of lipoxidase was incorporated into liposomes. The yield of thiobarbituric acid react...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715769900300521
更新日期:1999-06-01 00:00:00
abstract::Individuals with low serum cholesterol experience greater than expected age-adjusted mortality from non-atherosclerotic diseases, including cancer, respiratory and digestive illnesses, but the basis for these associations remains unclear. The current investigation considered the hypothesis that hypocholesterolemia is ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769609149049
更新日期:1996-09-01 00:00:00
abstract::Carotenoids scavenge simple lipid-like alkylperoxyl radicals. However, the rate constant is too low to be determined directly and the mechanism is likewise not known with certainty [Mortensen, A. and Skibsted, L.H. (1998) FEBS Lett. 426, 392-396]. It is demonstrated that carotenoids react with peroxyl radicals only sl...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760290006501
更新日期:2002-02-01 00:00:00
abstract::Flavonoids, which are dietary components and have possible drug uses, inhibit lipoprotein oxidation in vitro. The present study considered whether flavonoid supplementation in humans could influence lipoprotein vulnerability to oxidation. Citrus flavonoid supplementation (about 1g/day, 3 weeks), or placebo, was given ...
journal_title:Free radical research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1080/10715769900300341
更新日期:1999-04-01 00:00:00
abstract::Oxidatively induced damage caused by free radicals and other DNA-damaging agents generate a plethora of products in the DNA of living organisms. There is mounting evidence for the involvement of this type of damage in the etiology of numerous diseases including carcinogenesis. For a thorough understanding of the mecha...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2015.1014814
更新日期:2015-05-01 00:00:00
abstract::S-Nitrosation plays an important role in regulation of protein function and signal transduction. Discovering S-nitrosated targets is a prerequisite for further functional study. However, current proteomic methods used to quantify S-nitrosation are limited in their applicability to certain types of samples, or by the n...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2012.684244
更新日期:2012-08-01 00:00:00
abstract::Nitration-induced protein damage in the placenta leads to impaired blood flow and deficient feto-placental exchange in diabetic pregnancies. This work studied the effect of nitric oxide and peroxynitrite on Cu/Zn SOD activity in rat placentas and evaluated whether Cu/Zn SOD is nitrated in the placenta from diabetic ra...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2010.512039
更新日期:2010-12-01 00:00:00
abstract::Reactive oxygen species (ROS) have been poised at a straddled state of being beneficiary as well detrimental depending on its threshold levels. Maintaining the homeostasis of ROS is imperative for normal cellular physiology, wherein physiological concentrations of ROS are involved in cell signaling and elevated ROS co...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2016.1155708
更新日期:2016-01-01 00:00:00
abstract::In this study, three rapid assay techniques for the determination of glutathione, one enzymatic, one fluorometric and one newly patented colorimetric method, were compared by measuring reduced (GSH) and oxidized (GSSG) glutathione in guinea-pig heart and liver. The HPLC technique was used as a standard, since it is co...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769709084481
更新日期:1997-05-01 00:00:00
abstract::Weaning mice were fed a diet supplemented with beef tallow (BT) or BT plus docosahexaenoic acid (DHA) containing 100 mg alpha-tocopherol/kg (alpha-Toc100) or 500 mg alpha-tocopherol/kg (alpha-Toc500) for 4 wk to modify membrane fatty acid unsaturation, and then were administered ferric nitrilotriacetate (Fe-NTA). The ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715769900300221
更新日期:1999-03-01 00:00:00
abstract::Several papers have claimed that mitochondria contain nitric oxide synthase (NOS) and make nitric oxide (NO*) in amounts sufficient to affect mitochondrial respiration. However, we found that the addition of L-arginine or the NOS inhibitor L-NMMA to intact rat liver mitochondria did not have any effect on the respirat...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760410001694008
更新日期:2004-06-01 00:00:00
abstract::The effect of antioxidants on ammonia induced CNS and renal pathobiology in 10 sheep infested by L. Cuprina larvae was investigated. The condition produces severe dermatitis, proliferation of macrophages and hyperammonaemia, and free radicals may therefore be involved in the pathogenesis. Five of the sheep (treated gr...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769409056553
更新日期:1994-07-01 00:00:00
abstract::Penicillins, as bactericidal antibiotics, have been widely used to treat infections for several decades. Their structure contains both aromatic and thioether moieties susceptible to free radical oxidation. The (•)OH induced oxidation mechanism of amoxicillin was investigated by pulse radiolysis techniques and by final...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1100729
更新日期:2016-01-01 00:00:00
abstract::Lectin-like oxidized low-density lipoprotein (LOX-1) has been identified in endothelial cells as the main receptor of oxidized low-density lipoprotein (OxLDL). LOX-1 is upregulated in the presence of pathological conditions including atherosclerosis, hypertension, and diabetes because it acts as a mediator of "endothe...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2014.929122
更新日期:2014-08-01 00:00:00
abstract::To examine the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) in the oxidative stress-induced increase of permeability in endothelial cells, the effects of a p38 MAPK inhibitor (SB203580) and ERK inhibitor (PD90859) on the H2O2-induced increase of permeab...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760100301531
更新日期:2001-11-01 00:00:00
abstract::Free radical oxidation of cholesterol and its precursors contribute significantly to the pathophysiology of a number of human diseases. This review intends to summarize recent developments and provide a perspective on the reactivities of sterols toward free radical oxidation, the free radical reaction mechanism, and t...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2014.985219
更新日期:2015-01-01 00:00:00
abstract::It is well known that reactive oxygen species (ROS) attack several living tissues and increase the risk of development and progression of serious diseases. In neuronal level, ROS induce cell death in concentration-dependent fashion. However, little is known about the mechanisms of neuronal changes by ROS prior to indu...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2011.647689
更新日期:2012-02-01 00:00:00
abstract::Tropolones, the naturally occurring compounds responsible for the durability of heartwood of several cupressaceous trees, have been shown to possess both metal chelating and antioxidant properties. However, little is known about the ability of tropolone and its derivatives to protect cultured cells from oxidative stre...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760400017244
更新日期:2005-02-01 00:00:00
abstract::Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1061186
更新日期:2015-10-01 00:00:00
abstract::The intestinal tract, known for its capability for self-renew, represents the first barrier of defence between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/T...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2011.611509
更新日期:2011-11-01 00:00:00
abstract::In the present study we tested the ability of different antioxidant agents, used alone or in combination, to reduce the reactive oxygen species (ROS) levels and to increase the glutathione peroxidase (GPx) activity. Moreover, we tested the ability of such antioxidant agents to reduce the serum levels of proinflammator...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760303849
更新日期:2003-02-01 00:00:00
abstract::The effects of various free radicals derived from 6-formylpterin (6-FP), alpha-phenyl-tert-butyl nitrone (PBN) and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) combined with hyperthermia, on gene expression in similarly enhanced apoptosis of human lymphoma U937 cells were investigated using cDNA microarrays c...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760600946432
更新日期:2007-01-01 00:00:00
abstract::The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 ...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.3109/10715762.2011.571685
更新日期:2011-06-01 00:00:00
abstract::The protecting ability of the Piper betle leaves-derived phenol, allylpyrocatechol (APC) against AAPH-induced membrane damage of human red blood cells (RBCs) was investigated. Compared to control, AAPH (50 mM) treatment resulted in significant hemolysis (55%, p < 0.01), associated with increased malondialdehyde (MDA) ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.816847
更新日期:2013-09-01 00:00:00
abstract::In cells, NADH and NADPH are mainly bound to dehydrogenases such as lactate dehydrogenase (LDH). In cell-free systems, the binary LDH-NADH complex has been demonstrated to produce reactive oxygen species via a chain oxidation of NADH initiated and propagated by superoxide. We studied here whether this chain radical re...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760500231786
更新日期:2005-10-01 00:00:00