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 Pub date
2008-11-27

Asbestos cancer and cancer-causing genes

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Asbestos cancer and cancer-causing genes
Asbestos is a general term for natural mineral fiber. Long-term exposure to asbestos can cause lung cancer and mesothelioma. Since the proposed asbestos and lung cancer, the use of in vitro and in vivo systems, asbestos fibers from the physical characteristics of the chemical composition of the cell toxicity, genetic toxicity, cancer genes and tumor suppressor genes, and so, from the body, cells, Health , A multi-level, and other elements to explore the mechanism of cancer-causing asbestos. This article will asbestos cancer and cancer-causing genes are reviewed.

Oncogenes and tumor suppressor gene regulation of cell proliferation plays an important role: to promote cancer cell proliferation genes and prevent their occurrence of terminal differentiation; tumor suppressor gene to promote mature cells to terminal differentiation and finally died away. Maintain the dynamic balance of these two types of genes, the normal cell proliferation and death precise control, once the destruction of the relationship between the two is bound to lead to cell proliferation regulation of cell disorder caused malignant change [1]. Asbestos cancer-causing mechanism of the initial concentration of asbestos in the physical and chemical characteristics of cell toxicity, genetic toxicity, and so on. With the discovery of the cancer gene, cell transformation in the importance of attention. In the late 80's, it began with the cancer-causing asbestos cancer gene relations.

Asbestos can induce cell chromosome aberration, when the cancer gene involved distortion or tumor suppressor gene located on chromosome, such as common first 1,3,4,5,7,9,11,13,17,22 chromosome [2 , 3], it could lead to the activation of oncogenes and tumor suppressor gene inactivation.

First, cancer-causing asbestos and cancer gene

Asbestos-related tumors of the long incubation period, malignant mesothelioma of the incubation period of up to 40 years, suggesting that cancer cells involved in the process of multi-locus of change [4]. Although the discovery of a large number of cancer genes, but the asbestos-related tumors in the study only focused on the oncogene ras, c-fos, c-jun, sis, and so on.

Asbestos cancer and cancer-causing gene study on the relationship between, on the ras gene of an earlier in-depth study. Annab, and so on [5] of asbestos-induced Syrian hamster tumor cells have been studied and found in the tumor-derived (derived) cell lines, about 50% of the H-ras gene activation in the control group of non-cancerous cell lines The lack of H-ras gene activity. The activation of H-ras gene transfer of human skin cells and normal cells, and then inoculated mice transfected cells can be induced tumors, and without the H-ras gene transfer of cancer cells in mice can not make the tumor [6] . Brandt-Rauf, etc. [7] from the beginning of 1983, 36 cases of lung asbestos and silicosis were 10 cases of follow-up to 1991, found 18 cases for the development of tumors (of which 11 cases of lung cancer, 2 cases of pleural mesothelioma) . Serum of patients in the ras gene p21 protein product testing and found that 5 cases of patients with lung cancer and mesothelioma 2 cases of patients with elevated levels of p21 (7 / 18); not for the development of tumors in 28 patients, only 2 cases higher levels of p21 (2 / 28), the difference was significant (P = 0.012). Vainio, etc. [8] in the study of K-ras gene mutation in a higher frequency of lung cancer in asbestos and the impact of smoking, they found K-ras gene mutation in patients with lung in asbestos-related content. Asbestos cancer cells in the process of target cells caused by the transformation and immortalization, but the H-ras gene mutations in cancer cells, often after. Barrett [9] that: H-ras gene mutation may not be a direct result of the role of asbestos. Lamb, and so on [10] 3 from the individual organizations mesothelioma isolated DNA, transfer NIH/3T3 cells did not tumorigenic. From isolated tumor DNA, re-transfer of the 5-week incubation period to carry out evaluation of carcinogenicity, indicating a high positive. Using Southern blot analysis of the NIH/3T3 cell DNA, found that H-ras, K-ras and N-ras gene and the mouse gene are highly homologous, that is not detected human gene mesothelioma. However, repeated use of Alu sequences (unique to the human sequence) DNA probe to detect the true test of the initial and re-transfer of DNA containing the human sequence. These results show that: people with mesothelioma by the activation of the ras gene may not belong to the family. Metcalf, and so on [11] by PCR amplification directly after the determination of the genome sequence of the method of inspection of the 17 individuals from 20 mesothelioma cell K-ras gene codon 12,13,61 single base changes in the frequency, not Found that K-ras gene mutation.

Mossman laboratory in the United States in 1993 and the beginning of asbestos in target cells c-fos and c-jun expression had an in-depth research. c-fos and c-jun is a group of early response gene family, in the growth factor, tumor promoting factors, etc., this first group of gene transcription, through its product code to start cell division and the transcription of other genes, to Cells from G1 phase to enter S phase, to accelerate cell proliferation. Expression disorder can cause abnormal cell proliferation and transformation [12].

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