Interaction of erythrocyte membranes with particulates.

Ottolenghi, Abramo C.; Joseph, Laurie B.; Newman, Howard; Stephens, R. E.

doi:10.1289/ehp.8351253

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…This is probably associated with the hemolytic action of chrysotile which was previously reported. (35) It is interesting to note that not only the spleen but also the liver and kidney are oxidatively stressed 4 weeks after administration of each asbestos fiber type (Fig. 6).…”

Section: Discussionmentioning

confidence: 97%

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: 97%

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

et al. 2008

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“…Chrysotile is not easily removed from in vitro by normal cell handling techniques (i.e., feeding and passaging). Chrysotile may become adsorbed to the cell membrane (6) or ingested into the cell.…”

Section: Discussionmentioning

confidence: 99%

Morphological transformation in vitro of normal human fibroblasts by chrysotile.

Joseph¹,

Stephens²,

Ottolenghi³

et al. 1983

Environ Health Perspect

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Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies.Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due-at least in part-to a lack of control over cytokinesis.

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“…For other gram-negative pathogens, resistance to tigecycline was reported in Acinetobacter baumannii [ 185 , 221 – 224 ], as well as S. marcescens [ 211 ] and H. influenzae [ 211 ]. In gram-positive pathogens, tigecycline resistance was reported in two and three MRSA isolates from the Netherlands [ 225 ].…”

Section: Effectiveness Of Tigecycline In Clinical Settingsmentioning

confidence: 99%