Speaker
Dr
Galina Rusinova
(Southern Urals Biophysics Institute)
Description
Internal exposure to alpha-particle radiation from incorporated Pu-239 increases the risk of lung cancer. Studies including complex approaches on revelation gene alterations at different cancer stages are perspective. Tumor suppressor gene p53 is one of the most important gene regulating cellular cycle. Alterations of gene p53 play an important role in human carcinogenesis, and are observed approximately in 50 % of malignant neoplasms in human lung.
In this research the results of studies on mechanisms of lung cancer in Mayak workers exposed to internal alpha-radiation from incorporated Pu-239 are presented. Biospecimens of unaltered lung tissue and cases of proliferative, pretumor, and tumor changes of lung epithelium of Mayak workers were selected. To reveal the protein altered immunohistochemical analysis was conducted using antibodies for protein p53 in cases selected. Cells with mutative protein p53 were found in all cases of proliferative, pretumor, and tumor changes of lung epithelium. Heterogeneity of protein p53 accumulation was observed in cells of lung tissue with different degree of degeneration. Based on registry, concentration of cells with mutative protein p53 increased with the degree of dedifferentiation. Maximum protein p53 accumulation was registered in tumor cells. Occurrence of cells with mutative protein p53 allowed considering mutations in gene p53 and loss of it’s main function as “a genome guard”.
Studies on 5, 7, and 8 exons located in central region of gene p53 were conducted. These exons considered as high mutable because 90% of all mutations of gene p53 were revealed there. Searching for mutations in exons mentioned above was performed using TTGE and sequencing methods.
In spite of the fact that protein p53 was revealed in all proliferative, pretumor cases, mutative changes were found only in 20% of them. Mutations were found in 40% of all biospecimens of tumor tissue of lung selected for the study, in which mutative protein was revealed by immunohistochemical analysis. All mutations were revealed in the central region of gene p53 (5, 7, and 8 exons). According to the data obtained, in addition to mutative alterations in gene p53 posttranscriptional events leading to mutations in protein p53, such as splicing mutations or posttranscriptional alterations of mRNA activity with microRNA participation might be observed.
Primary authors
Dr
Galina Rusinova
(Southern Urals Biophysics Institute)
Dr
Maxim Guryanov
(Southern Urals Biophysics Institute)
