Experimental Lung Cancer in Hamsters

Gross, Paul; Tolker, Ethel B.; Babyak, Mary Ann; Kaschak, Marianne

doi:10.1080/00039896.1965.10664170

Cited by 13 publications

(3 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…None of 26 squamous lung cysts induced in rats following chronic exposure to diesel exhaust or carbon black were transplantable into nude mice (Mauderly et al, 1994). Thus, in the absence of criteria of malignancy-true invasion of structures such as the pleura or bronchi, and/or dysplasia-these lesions should not be considered neoplastic (Baskerville et al, 1974;Gross et al, 1965), although transformation to carcinoma may occur. …”

Section: Proliferative Responsesmentioning

confidence: 98%

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Schultz

1996

Inhalation Toxicology

View full text Add to dashboard Cite

The proper interpretation of animal experiments on particulate materials i s essential in order to properly identify the relative risk associated with human exposure to these materials. This article reviews the pathology of experimental dust-induced pulmonary lesions, discusses factors necessary for the proper interpretation of these results, and makes recommendations for the design and conduct of future studies. In experimental studies, animals are often exposed to high concentrations of dusts that overwhelm normal lung clearance mechanisms, resulting in the somewhat poorly defined condition of "dust overload." The pulmonary response to this intra-alveolar dust loading is nonspecific and thus morphologically similar regardless of the dust type studied. In the rat, these lesions are characterized by alveolar macrophage accumulation, necrosis of pneumocytes, granuloma formation, fibrosis, and bronchiolarization and squamous metaplasia of alveoli. Depending on exposurz concentration and duration, bronchiolealveolar ademonas and adenocarcinomas and cystic keratinizing squamous lesions may occur. The squamous lesions appear to represent a response unique to the rat. The significance of studies using dust concentrations that produce these nonspecific lesions is questionable since such conditions, with extreme exception, do not occur in humans. Further, fibrogenic or carcinogenic properties that may be specific to a particular dust at exposure concentrations relevant to humans may actually be masked by the nonspecific response that occurs following dust overload. Studies with dust at concentrations that produce an interstitial dust loading but that are below the threshold for intra-alveolar dust overload are more relevant for human health hazard identification. This has been best demonstrated by the results of numerous studies with asbestos in rats where fibrosis and neoplasia, morphologically similar to that seen in humans, have been produced in the absence of the nonspecific lesions seen in dust overload. The interpretation of studies where dusts are administrated by nonconventional routes should also be undertaken with caution. for example, serosa tests bypass an important mechanistic step in fiber-induced mesothelioma, namely, the ability of a dust to reach the pleura surface following inhalation. In addition, such tests may produce diagnostic dilemmas since reactive changes on serosal surfaces, which are expected following application of any foreign substance, may be difficult to differentiate from a neoplastic response. Future studies to assess the human health hazards of fibrous and nonfibrous dusts should be conducted at concentrations that allow for the characterization of responses specific to a given dust and by exposure routes most representative of that experienced by humans.

show abstract

Section: Proliferative Responsesmentioning

confidence: 98%

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Schultz

1996

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…Polymerization in the liver is associated with cirrhosis, and the accompanying plasma deficiency leaves the lungs exposed to neutrophil elastase resulting in premature emphysema ( 17 , 33 , 36 , 47 , 54 ). The association of Z-AT with emphysema and the finding that proteinases could cause experimental emphysema in small animals were critical in initiating the proteinase:antiproteinase theory of emphysema ( 22 ).…”

mentioning

confidence: 99%

Oxidized α₁-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema

Li¹,

Alam²,

Wang³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

α1-Antitrypsin (AT) is a major elastase inhibitor within the lung. Oxidation of critical methionine residues in AT generates oxidized AT (Ox-AT), which has a greatly diminished ability to inhibit neutrophil elastase. This process may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD) by creating a functional deficiency of AT permitting lung destruction. We show here that Ox-AT promotes release of human monocyte chemoattractant protein-1 (MCP-1) and IL-8 from human lung type epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells. Native, cleaved, polymeric AT and secretory leukoproteinase inhibitor (SLPI) and oxidized conformations of cleaved, polymeric AT and SLPI did not have any significant effect on MCP-1 and IL-8 secretion. These findings were supported by the fact that instillation of Ox-AT into murine lungs resulted in an increase in JE (mouse MCP-1) and increased macrophage numbers in the bronchoalveolar lavage fluid. The effect of Ox-AT was dependent on NF-κB and activator protein-1 (AP-1)/JNK. These findings have important implications. They demonstrate that the oxidation of methionines in AT by oxidants released by cigarette smoke or inflammatory cells not only reduces the antielastase lung protection, but also converts AT into a proinflammatory stimulus. Ox-AT generated in the airway interacts directly with epithelial cells to release chemokines IL-8 and MCP-1, which in turn attracts macrophages and neutrophils into the airways. The release of oxidants by these inflammatory cells could oxidize AT, perpetuating the cycle and potentially contributing to the pathogenesis of COPD. Furthermore, these data demonstrate that molecules such as oxidants, antiproteinases, and chemokines, rather than act independently, are likely to interact to cause emphysema.

show abstract

“…Numerous studies of the tumourigenic effects of benzo[a]pyrene and mixtures of substances containing benzo[a]pyrene used intratracheal instillation as the form of administration to induce benign and malignant tumours. The golden hamster was the main animal species used (Farrell and Davis 1974;Feron 1972;Feron et al 1973Feron et al , 1980Gross et al 1965;Henry et al 1973Henry et al , 1975Herrold and Dunham 1962;Hilfrich et al 1973;Ketkar et al 1979;Kobayashi 1975;Montesano et al 1974;Pott et al 1973Pott et al , 1979Pott and Stöber 1983;Saffiotti et al 1965Saffiotti et al , 1967Saffiotti et al , 1968Sellakumar et al 1976;Smith et al 1970;Stenbäck et al 1975;Stenbäck and Rowland 1978;Thyssen et al 1980). Only few studies are available with rats (Bogovski et al 1982;Davis et al 1975;Pylev and Shabad 1973;Shabad 1971).…”

Section: B) After Intratracheal Instillationmentioning

confidence: 99%

Polycyclic aromatic hydrocarbons, carcinogenic (PAH) [MAK Value Documentation, 2012]

2013

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Published in the series MAK Value Documentations , Vol. 27 (2012) The article contains sections titled: Formation of PAH Relative proportions of PAH (PAH profiles) Significance of benzo[ a ]pyrene (BaP) Carcinogenicity of benzo[ a ]pyrene a) After implantation in the lungs b) After intratracheal instillation c) After inhalation d) After application to the skin e) After other types of treatment Carcinogenicity of other PAH Carcinogenicity of the PAH fractions of pyrolysis products The question of a standard for the carcinogenic potential of PAH fractions

show abstract

Experimental Lung Cancer in Hamsters

Cited by 13 publications

References 2 publications

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Oxidized α₁-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema

Polycyclic aromatic hydrocarbons, carcinogenic (PAH) [MAK Value Documentation, 2012]

Contact Info

Product

Resources

About

Experimental Lung Cancer in Hamsters

Cited by 13 publications

References 2 publications

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

Oxidized α1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema

Polycyclic aromatic hydrocarbons, carcinogenic (PAH) [MAK Value Documentation, 2012]

Contact Info

Product

Resources

About

Oxidized α₁-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema