Asbestos Selected Cancers (2006) / Chapter Skim
Currently Skimming:
5 Biological Aspects of Asbestos Related Diseases
5 Biological Aspects of Asbestos Related Diseases
Pages 81-103
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 81... ...
Those mechanisms will be discussed in detail after a brief summary of the clinical features and risk factors of lung cancer and malignant mesothelioma. Asbestos-Related Diseases The International Agency for Research on Cancer (IARC 1987)
|
From page 82... ...
Risk Factors for Lung Cancer and Malignant Mesothelioma Tobacco-smoking is a major causal risk factor for lung cancer (Table 5.2) and risk of developing lung cancer in current or former smokers is greatly increased by exposure to asbestos fibers.
|
From page 83... ...
. Malignant mesotheliomas have also been reported in people with inherited cancer-susceptibility syndromes following exposure to asbestos fibers or radiation therapy (Table 5.4)
|
From page 84... ...
Although mutations in the p53 tumor-suppressor gene are generally rare in human malignant mesotheliomas (Metcalf et al.
|
From page 85... ...
. Mechanisms of Asbestos Carcinogenicity On the basis of extensive work with in vitro model systems and animal models of asbestosis, lung cancer, and mesothelioma, direct and indirect mechanisms for fiber carcinogenicity have been proposed.
|
From page 86... ...
Both chronic and acute exposure to asbestos fibers increases the proliferation of epithelial and mesothelial cells. Nongenotoxic mechanisms leading to increased cell proliferation include activation of growth factor receptors and intracellular signaling pathways (reviewed in Albrecht et al.
|
From page 87... ...
2001) and in human malignant mesotheliomas (Hirao et al.
|
From page 88... ...
. SV40 viral DNA sequences and oncoproteins have been detected in human pleural malignant mesotheliomas by some investigators (reviewed by Gazdar et al.
|
From page 89... ...
Several studies have failed to detect SV40 viral DNA sequences in human malignant mesotheliomas (López-Ríos et al. 2004, Manfredi et al.
|
From page 90... ...
. SV40 virus also induces telomerase activity and immortalization of human mesothelial cells (Foddis et al.
|
From page 91... ...
(1994a) exposed F344 rats to crocidolite asbestos at 10 mg/m3 in a chronic study to compare the response to asbestos with that to slag wool insulation fibers.
|
From page 92... ...
In neither species did chronic asbestos exposures by inhalation lead to tumors in the oropharyngeal region, the gut, or the larynx. Ingestion Toxicity Studies One report of the toxicity of ingested asbestos involved F344 rats exposed to asbestos in combination with subcutaneous administration of a known intestinal carcinogen, azoxymethane (AOM)
|
From page 93... ...
The studies do not indicate an association between ingested asbestos and neoplasia. Summary On the basis of animal studies of asbestos exposure in rats and Syrian hamsters, one would not expect exposure to asbestos fibers at environmental or even occupational concentrations to increase the incidence of tumors in the oropharyngeal region, the larynx, or the gut.
|
From page 94... ...
There seems to be no evidence that definitively identifies a biomarker of asbestos exposure that predicts cancers of the larynx, pharynx, esophagus, stomach, colon, or rectum. Animal Studies Human malignant mesotheliomas are induced by fibrous dusts, but the nature of the interactions between fibers and target cells, including the molecular mechanisms leading to tumorigenesis, are not fully understood.
|
From page 95... ...
These intriguing data suggest that there is a gradient in the concentrations of 8-OHdG in white blood cells between asbestos-exposed patients with and without cancer and non-asbestos-exposed controls. There has been extensive work on several DNA-inducible genes as biomarkers of exposure to these agents, including p53 induction of DNA strand breaks, p53 expression, and apoptosis in cell lines, particularly in cultured mesothelial cells.
|
From page 96... ...
2002. Neurofibromatosis 2 and malignant mesothelioma.
|
From page 97... ...
1996. Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species.
|
From page 98... ...
2002. SV40 infection induces telomerase activity in human mesothelial cells.
|
From page 99... ...
locus in human malignant mesothelial tumors. Carcinogenesis 23(7)
|
From page 100... ...
p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer.
|
From page 101... ...
1997. Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers.
|
From page 102... ...
1997. Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma.
|
From page 103... ...
1999. Presence of simian virus 40 sequences in malignant mesotheliomas and mesothelial cell proliferations.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.