Conjunction of the molecular, cytogenetic and genetic biomarkers as predictor of vulnerability to medical radiation treatment

Abstract

In previously reported studies of healthy controls, prostate cancer patients, and thyroid disease patients, exposed diagnostically to I-131, voluntarily obtained blood samples, or isolated lymphocytes were exposed in vitro to high challenging dose of X-rays. Before and right after in vitro irradiation; the DNA Repair Competence Assay and cytogenetic methods were applied. Strong variability between individual vulnerability to radiation was reported. For this investigation, using PCR method the XRCC1(194) and XRCC1(399), that are engaged in base excision and DNA single strand breaks repair, and XRCC3(241) involved in DNA double strand breaks repair via homologous recombination, were investigated in randomly chosen samples from 60 subjects. Results of investigated biomarkers stratified according conjunction of polymorphic alleles have shown insignificant variability between all subjects in the DNA sensitivity to irradiation, detected immediately after challenging exposure in 40 °C. In contrast, high differences are observed between subgroups stratified according conjunction of polymorphic alleles of investigated genes, in levels of biomarkers related to DNA repair (DNA RCA and percentage of cells with significantly elevated number of sister chromatid exchanges) as well as biomarkers of cancer risk. One of the highest percentage of not repaired DNA damage evaluated by the DNARCA, and frequency of chromosome aberration, were detected in lymphocytes of prostate cancer patient with homozygous genotype at XRCC3-241/C and XRCC1-194/C, and heterozygous at XRCC1-399A/G locus. Obtained results confirm strong influence of genotypes on the repair efficiency of DNA damage induced by irradiation and levels of biomarkers that are predictor of cancer risk.