Pathological investigation of oxidative stress in the post‐genomic era

Toyokuni, Shinya; Akatsuka, Shinya

doi:10.1111/j.1440-1827.2007.02127.x

Cited by 38 publications

(27 citation statements)

References 176 publications

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“…(15,25) In the present paper, we not only re-evaluated the catalytic activities of UICC asbestos fibers for the generation of free radicals but also identified several novel characteristics of these fibers in asbestos-induced oxidative DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

et al. 2008

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Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H 2 O 2 , which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5′-triphosphate and guanosine 5′-triphosphate, did not inhibit this reaction. Second, we used time-lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT-5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8-hydroxy-2′-deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron. (Cancer Sci 2008; 99: 2142-2151) A sbestos fibers have been heavily used in industry from World War II to the present because of their durability, heat-resistance and low cost.(1,2) However, in 1987, the International Agency for Research on Cancer (IARC) designated asbestos fibers as a group I (definite) carcinogen for humans (http:// monographs.iarc.fr/ENG/Classification/crthgr01.php), and asbestos fibers were banned in many European and North American countries in the 1990s.(1,2) In June of 2005, asbestos-associated deaths suddenly attracted social attention in Japan because it was reported that 79 people who worked in factories using asbestos had been killed by an asbestos-associated rare cancer called diffuse malignant mesothelioma (DMM) over the past 26 years. Furthermore, people who lived near those factories also suffered from the same fatal disease.(4) The characteristics of DMM are as follows: (i) it is associated with repeated asbestos exposure; (5,6) (ii) once diagnosed, prognosis is poor; (7) and (iii) it takes 30-40 years after the start of asbestos exposure for DMM to occur.(5,6) It is expected that the incidence of DMM in Japan will peak in 2025 with 100 000 predicted deaths from this neoplasm. (8) There are several hypotheses a...

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Section: Discussionmentioning

confidence: 99%

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

et al. 2008

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“…Reactive oxygen species generated during normal cellular metabolism and in response to exogenous genotoxins lead to DNA base damage (Feig et al, 1994;Bjelland and Seeberg, 2003;Toyokuni and Akatsuka, 2007). The predominant DNA repair pathway that removes oxidized and alkylated bases is the BER pathway.…”

Section: Discussionmentioning

confidence: 99%

XRCC1 rs25487 polymorphism is associated with lung cancer risk in epidemiologically susceptible Chinese people

Wang

Zhao

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Base excision repair (BER) plays an important role in maintaining genome integrity and anti-cancer drug resistance. Single nucleotide polymorphisms (SNPs) in BER genes were detected in 500 lung cancer patients and 500 cancer-free controls. A logistic regression model was applied to analyze the relationship between lung cancer susceptibility and BER SNPs coupled with a wide range of epidemiological factors in a Chinese population. SNPs including rs25487 in the X-ray repair crosscomplementing group 1 gene, rs1052133 in the 8-oxoguanine DNA glycosylase gene, and rs1136410 in the poly (ADP-ribose) polymerase 1 gene were identified. Multivariate analysis showed that the rs25487-AG genotype was associated with a higher incidence of lung cancer compared with the GG genotype. The rs25487 SNP was associated with the pathological distribution of lung cancer. Moreover, rs1052133-GG was associated with early age of lung cancer onset compared with the CC genotype. Our data demonstrated that the SNPs rs25487 and rs1052133 are risk factors for lung cancer in epidemiologically susceptible Chinese people.

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“…It has been repeatedly suggested and demonstrated that exposure of cells to low levels of ROS induces division and proliferation, higher levels induce apoptosis and still higher necrosis (for a review see [63]). Such experiments do not match the complexity of situation in vivo where ROS signaling may involve short localized pulses of ROS nevertheless may reflect some general principles of ROS action.…”

Section: Cell Proliferationmentioning

confidence: 99%