Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Bartsch, H.; Malaveille, C.; Barbin, Alain; Bresil, H.; Tomatis, L.; Montesano, R.

doi:10.2307/3428625

Cited by 11 publications

(7 citation statements)

References 15 publications

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“…At that time, a thriving literature was available on the roles of mixed function oxidases in redox bioactivation of xenobiotics (Szybalski and Iyer , 1964 ;Bartsch et al , 1976 ;Pegg , 1980 ). Nevertheless, the crosslinker sensitivity was not related to redox activities in those early studies, nor it seems to be integrated within the mechanistic frame of FA defect after the subsequent investigations that demonstrated the sine qua non requirement of redox bioactivation of FA-related xenobiotics (Joenje and Oostra , 1986 ;Pritsos and Sartorelli , 1986 ;Dusre et al , 1990 ;Boogaard and Bond , 1996 ;Clarke et al , 1997 ;Vlachodimitropoulos et al , 1997 ;Span ò et al, 1998 ;Erexson and Tindall , 2000 ;Barouki and Morel , 2001 ;Penketh et al , 2001 ;Schaaf et al , 2002 ).…”

Section: Summary and Historical Remarksmentioning

confidence: 99%

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management

Pagano

Talamanca

Castello

et al. 2012

Biological Chemistry

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Fanconi anaemia (FA) is a genetic disease featuring bone marrow failure, proneness to malignancies, and chromosomal instability. A line of studies has related FA to oxidative stress (OS). This review attempts to evaluate the evidence for FA-associated redox abnormalities in the literature from 1981 to 2010. Among 2170 journal articles on FA evaluated, 162 related FA with OS. Early studies reported excess oxygen toxicity in FA cells that accumulated oxidative DNA damage. Prooxidant states were found in white blood cells and body fl uids from FA patients as excess luminol-dependent chemiluminescence, 8-hydroxy-deoxyguanosine, reduced glutathione/ oxidized glutathione imbalance, and tumour necrosis factor-α . Some FA gene products involved in redox homeostasis can be summarized as follows: (a) FANCA , FANCC , and FANCG interact with cytochrome P450-related activities and/or respond to oxidative damage; (b) FANCD2 in OS response interacts with forkhead box O3 and ataxia telangiectasia mutated protein; (c) FANCG is found in mitochondria and interacts with PRDX3, and FA-G cells display distorted mitochondria and decreased peroxidase activity; (d) FANCJ ( BACH1/BRIP1 ) is a repressor of haeme oxygenase-1 gene and senses oxidative base damage; (e) antioxidants, such as tempol and resveratrol decrease cancer incidence and haematopoietic defects in Fancd2 -/-mice. The overall evidence for FA-associated OS may suggest designing chemoprevention studies aimed at delaying the onset of OS-related clinical complications.

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Section: Summary and Historical Remarksmentioning

confidence: 99%

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management

Pagano

Talamanca

Castello

et al. 2012

Biological Chemistry

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“…It was interesting that the ultrastructural changes seen in Clara cells and to some extent in the ciliated cells were similar to those of hepatic cells of animals exposed to vinyl chloride; cellular hypertrophy and proliferation of the endoplasmic reticulum were common responses, seen in both the bronchiolar epithelium and the hepatic cells. The endoplasmic reticulum of the hepatic cells has been suggested as the site where vinyl chloride is metabolized, to be transformed into a chemically reactive metabolite which is the' ultimate carcinogen (36,(41)(42)(43)(44)(45). Although it has not been shown that lung has the capacity to metabolize the chemical to produce the carcinogen; if it were so, the bronchiolar cells, particularly Clara cells, may provide this mechanism: the cells are normally equipped with well-developed smoothsurfaced endoplasmic reticula and the organelles have shown a proliferative response after mice are exposed to vinyl chloride.…”

Section: Discussionmentioning

confidence: 99%

Neoplastic and nonneoplastic effects of vinyl chloride in mouse lung

Suzuki¹

1981

Environ Health Perspect

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Neoplastic effects of vinyl chloride were studied in lungs of 27 mice exposed to vinyl chloride monomer at 2500 and 6000 ppm for 5 and 6 months (large doses and long-term exposure). Pulmonary tumors were observed in 26 of 27 experimental animals. Light microscopy showed the tumors to be multiple and arranged in either tubulo-papillary or adenomatous formations. Although occasional mitotic divisions and invaginations into the bronchiolar lumen were observed, no metastases were found. By electron microscopy, short microvilli, tight junctions between two adjacent cells, appearance of osmiophilic lamellar bodies, large mitochondria of irregular shape, well developed Golgi complexes, continuous or discontinuous basement membranes, occasional appearance of “sequestration” and of crystalloids and lack of both cilia and mucous secretory granules were observed as characteristic features of the neoplastic cells. Some of the cells were poorly differentiated and were equipped with poorly developed organoids, without formation of osmiophilic lamellar bodies. The pulmonary tumors corresponded to “alveologenic” tumors. It is suggested that the neoplastic cells were transformed from type II alveolar epithelium via its hyperplastic form. Nonneoplastic effects of the chemical were also studied in the 27 mice. Major light microscopic alterations observed were proliferation and hypertrophy of the terminal bronchiolar cells, consisting of ciliated and Clara cells, hypersecretion of the epithelial mucin in the goblet cells of both the bronchial and the proximal bronchiolar epithelium, hyperplasia of alveolar epithelium, mobilization of alveolar macrophages and occasional presence of peribronchial or bronchiolar chronic inflammation. Electron microscopically, Clara cells of the terminal bronchiolar epithelium showed proliferation of the rough and smooth surfaced endoplasmic reticulum and appearance of large and abnormally shaped mitochondria. Similar alterations were found in the ciliated cells. Submicroscopic changes of pulmonary alveoli were represented by focal thickening of the basement membrane, multiple foci of hyperplastic type II cell (the precondition of the alveologenic tumor), active discharge of osmiophilic lamellar bodies from the type II cell and phagocytosis of the bodies by macrophages, appearance of cholesterol crystalloids in the macrophages, degeneration of alveolar septal cells and occasional appearance of a large nucleus with swelling of the capillary endothelium. The neoplastic effect of vinyl chloride of smaller doses (100, 10, 1 and 0 [control] ppm) and shorter exposure (four weeks) was studied in lungs of 120 mice. Our preliminary observation indicated that sacrificed animals at 40 weeks after the exposure showed productions of the alveologenic tumor in 5 of 9 (100 ppm), 2 of 9 (10 ppm), 1 of 9 (1 ppm) and 0 of 10 (control = 0 ppm). A dose-response relation was considered in the incidence of the alveologenic tumor production of vinyl chloride. It is concluded that mouse lung is an extremely sensitive indicator...

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“…The persistence of bromine in rat tissue for 24 hr following exposure to brominated fire retardants has been reported at this conference. The demonstration by Montesano of marked mutagenic assay activity by chloroprene (25) (greater than for vinyl chloride) should stimulate study of this monomer in human and animal tissue. Its nonchlorinated analog, butadiene, has a very rapid turnover in animal tissues following very high exposures, similar to that of styrene under the same conditions (26).…”

Section: October 1976mentioning

confidence: 99%

Evidence for existence in human tissues of monomers for plastics and rubber manufacture.

Wolff¹

1976

Environ Health Perspect

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Although exposure to many industrially important monomers is controlled by law, few of these reactive chemicals have been determined in human tissues. Analogy with other fat-soluble organic substances strongly implies that these monomers may be retained in tissue, suhject to the usual physiological constraints of metabolism, solubility and volatility. The storage of DDT and PCBs is discussed, as well as tetrachloroethylene (PCE) and trichloroethylene (TCE), which are chemically similar to many industrially used monomers. Styrene in blood and breath and its metabolites in urine have been studied in humans. Styrene and vinyl chloride have been measured in fat tissue of polymerization workers.Evidence for the presence of monomers and other unmetabolized organic materials in humans is surprisingly scarce, in spite of exposures to a large number of substances in the environment that are very fat soluble, and therefore prime candidates for prolonged body residence.Recent epidemiological and clinical field studies have been conducted by this laboratory among workers exposed to organic materials, including polymerization workers, anesthesiologists and workers making capacitors and transformers (PCB workers), and our interest has been directed toward the study of the storage and turnover in blood and adipose tissue of fat-soluble organic compounds.The distributional dynamics of many such compounds in the body can be derived using the compartmental model, with which anesthesiologists have studied uptake and elimination of anesthetics. Thus, during acute exposures (in anesthesia amounting to 1-2% of a halogenated anesthetic in breathing air) the bloodvessel rich organs and tissues are rapidly saturated due to high blood flow and medium solubility, while fat tissues are slowly saturated,

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Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Cited by 11 publications

References 15 publications

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management

Neoplastic and nonneoplastic effects of vinyl chloride in mouse lung

Evidence for existence in human tissues of monomers for plastics and rubber manufacture.

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