Molecular Characterization ofTP53Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

Abstract

Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i) a missense exchange in exon 4 (Arg72Pro); (ii) 2 synonymous exchanges, 1 in exon 5 (His179His), and another in exon 6 (Arg213Arg); (iii) 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511) and 1 in intron 8 (T → G at position 13.958). Alteration of codon 72 was found to be an important risk factor for cancer development (P = 0.024; OR = 6.48; CI: 1.29–32.64) when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

“…The wild-type TP53 gene normally responds to radiation with a high level of expression and subsequently mediates cell cycle arrest and DNA repair activation [33]. Therefore, TP53 is important for monitoring radiosensitivity to both high and low doses of radiation, alone or in combination with other stressors [18]. In this study, we failed to find an association between TP53 Arg72Pro polymorphism and radiosensitivity in people receiving the chronic low dose rate exposure.…”

“…Thus, individuals exhibiting TP53 72Arg will be more sensitive to ionizing radiation. In contrast, Brasil-Costa et al stated that individuals with homozygous proline coding alleles (C/C) genotype in codon 72 of exon 4 in TP53 gene are more radiosensitive and should be subjects for public health action in regions with environmental radioisotopes [18]. To validate this contradictory finding, here in this study we evaluated the correlation between TP53 Arg72Pro polymorphism and individual radiosensitivity using G 2 MN assay.…”

Molecular and <em>in silico</em> Study of TP53 Codon 72 Polymorphism (rs1042522) in a Population Exposed to High Background Radiation in Mamuju-West Sulawesi

“…People who live in areas with high environmental radioactivity levels and express the homozygous proline-coding allele (C/C) genotype for codon 72 of the tumor protein p53 gene (TP53) should be subjected to public health evaluations. Individuals with the C/C genotype are considered to be more sensitive to radiation exposure because proteins containing proline are less effective as transcription factors normally associated with the cell cycle, the activation of apoptosis, and the expression of genes related to DNA repair, which can lead to a reduced DNA damage repair capacity [4]. Cells with reduced DNA damage repair capacities are at risk of chromosomal instabilities, such as the development of dicentric chromosomes, acentric fragments, or micronucleus (MN) formation, that occur when chromosome fragments or whole chromosomes develop their own nuclear envelopes after failing to merge with daughter nuclei [5,6].…”