Asbestos A Complete Carcinogen Or Just A Promoter

Trying to better understand the mechanism of mesothelioma disease has been the goal of many researchers. Some believe that a threshold may exist between duration and intensity of asbestos exposure and the induction of mesothelioma. One interesting study is called, Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E. by S P Faux and P J Howden - Environ Health Perspect. 1997 September; 105(Suppl 5): 11271130. Here is an excerpt: Abstract - Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.

Another interesting article is called, Asbestos-related mesothelioma: epidemiological evidence for asbestos as a promoter by Browne K. - Arch Environ Health. 1983 Sep-Oct;38(5):261-6. Here is an excerpt: Abstract - A series of 144 cases of mesothelioma among asbestos workers indicated important divergences from the epidemiological pattern shown to exist for asbestos-related lung cancer. Consideration of exposure duration and intensity and the latent period between first exposure and death suggests that asbestos does not act as a complete carcinogen, but as a promoter. A threshold seems probable for both duration and intensity of exposure in the induction of mesothelioma. This threshold may, in part, be related to the passage of fibers from the lungs to the pleura or peritoneum, and would, in any case, be masked in lung cancer by the retention of asbestos in the lungs. Reported cases of mesothelioma in immediate family members indicate the existence of an additional factor in mesothelioma induction, acting earlier in life than the first asbestos exposure.

A third article worth examining is called, Conventional and high-resolution CT in asymptomatic asbestos-exposed workers By Pierre A. Gevenoisabc; P. De Vuystabc; S. Dedeireabc; J. Cosaertabc; R. Vande Weyerabc; and J. Struyvenabc - Acta Radiologica, Volume 35, Issue 3 May 1994 , pages 226 229. Here is an excerpt; Abstract - To compare the value of conventional CT (CCT) and high-resolution CT (HRCT) to detect benign asbestos-related diseases, 159 exposed workers with a normal chest radiography were imaged by both techniques. Pleural plaques were detected in a total of 59 cases (37.1%). Ten cases (16.9%) were detected by CCT only and one case (1.7%) by HRCT only. Pulmonary lesions compatible with parenchymal asbestosis were detected by HRCT in 20 cases, whereas CCT showed abnormalities in 45% of these. Rounded atelectasis was equally recognized by both techniques. The results confirm that in a subject with a normal chest radiography, HRCT is a better diagnostic tool to demonstrate lesions of asbestosis. On the other hand, HRCT is insufficient to exclude the presence of pleural plaques. When HRCT does not reveal pleural abnormalities, CCT should be performed.

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