The transcriptional activity of cell cycle and apoptosis genes in chronically exposed people with an increased frequency of TCR mutant lymphocytes

Quantitative assessment of gene expression of cell cycle (ATM, TP53, MDM2, CDKN1A) and apoptosis (BAX, BCL-2) was performed in 163 chronically exposed residents of the Techa riverside villages. Cumulative doses to red bone marrow in the study group ranged from 80 to 3510 mSv (mean 720 mSv). The control group consisted of 146 people resided in the same settlements under similar socio-economic conditions), but with exposure dose rate to red bone marrow not exceeded 1 mGy/year and cumulative doses to red bone marrow ˂70 mSv for the whole period of life, which corresponds to the levels of natural background radiation. The groups were comparable in sex and age and consisted of two ethnic groups: Turks - mostly Tatars, and Bashkirs, Slavs - mostly the Russians, as well as the Ukrainians and the Belarusians. Gene transcription 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. The most expressed changes in transcriptome in exposed individuals were observed for BCL-2 and BAX genes. Reduced activity was observed in CDKN1A and ATM genes of the exposed people with red bone marrow doses exceeded1000 mGy. Changes in the mRNA level of apoptosis-regulating genes were registered in people with increased frequency of TCR-mutant lymphocytes. The obtained data speak for the important role of apoptosis as the mechanism of maintained the genetic stability of cells after radiation exposure. Aberrant expression of apoptosis genes in people with increased frequency of TCR-mutant lymphocytes could be indicative of reduced effectiveness of the process 60-70 years after the chronic radiation exposure.