Chelyabinsk State University, Chelyabinsk, Russia
Russian Federation
GRNTI 34.49 Радиационная биология
Purpose: To study the levels of transcriptional activity of TP53 and MDM2 genes in the residents of the Techa riverside villages chronically exposed at a wide dose range. Material and methods: transcriptional activity of TP53 and MDM2 genes was assessed in 95 persons. The main study group included 80 people exposed to combined external and internal radiation (peripheral blood samples were taken 60–70 years after the beginning of chronic radiation exposure), mean accumulated dose to red bone marrow was 0.86 ± 0.08 Gy (doses varied in the range 0.1–3.65 Gy). The control group consisted of 15 people living in similar socio-economic conditions in the Southern Urals; the accumulated doses to red bone marrow did not exceed 0.07 Gy. Gene transcription activity profile was studied with real-time PCR assay. The data were analyzed using a comparative CT method with normalization to the “housekeeping” gene transcription in each sample. Statistical analysis was performed using the software PAST. Results and conclusion: In the course of the analysis we did not receive statistically significant differences between the study groups, but there was a tendency to a decrease in gene transcription in the group of exposed persons. The correlation analysis showed a weak negative dependence for TP53 and MDM2 genes, and this dependence was characterized not only by the accumulated dose value but was also associated with the age of the individuals under study. A tendency to a decrease in the transcription activity of the genes under study was noted when studying the effect of the dose. Statistically significant differences were shown for MDM2 gene in the group of individuals whose accumulated doses exceeded 2 Gy (p = 0.044). The analysis of age-peculiarities on gene transcription revealed a statistically significant decrease in TP53 gene transcription with increasing age of patients (p = 0.02). Non-radiation factors including smoking were also studied. The levels of gene transcription were compared between men and women of 2 main ethnicities (Bashkirs/Tartars and Slavs). Results of the study showed that neither sex nor ethnicity had any effect on the levels of TP53 and MDM2 gene transcription in the study groups. The effect of smoking on the activity of the genes under study was negligible.
chronic irradiation, gene expression, TP53, MDM2, low doses, radiobiological response
Воздействие ионизирующего излучения на организм человека индуцирует в нем комплекс реакций, начинающихся с молекулярного уровня организации и способных, в зависимости от вида, дозы и продолжительности облучения, приводить к определенным нарушениям на клеточном, тканевом и организменном уровне. В связи с этим в последние годы интенсивно изучается транскрипционная активность генов, вовлеченных в систему клеточного ответа после облучения. Одним из таких генов является ген ТР53, который кодирует транскрипционный фактор р53 и является супрессором злокачественных новообразований [1]. Нормальное функционирование белка р53 резко уменьшает вероятность накопления в организме аномальных клеток с различными изменениями генома, которые способствуют неопластической трансформации клеток и прогрессии возникших опухолевых клонов [2].
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