Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events

Abstract

It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of <0.1 Gy occurred at non-significant levels. The mutation spectrum in HPRT-deficient mutants revealed that the type of mutations induced by low-dose exposures was similar to that seen in spontaneous mutants. An apparent change in mutation type was observed for mutants induced by doses of >0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events.

Biological effects of low-dose γ-ray irradiation on chromosomes and DNA of Drosophila melanogaster

“…In contrast, the variation rate caused by HDR (>0.15 Gy) is considerably higher than that existing in Nature [ 7 ]. Moreover, the study indicated that the properties of mutations in the human hypoxanthine phosphoribosyltransferase ( HPRT ) gene are different [ 7 ].…”

“…Animal experimental studies indicate that exposure to LDR (typically doses of <200 mSv according to United Nations Scientific Committee on the Effects of Atomic Radiation [ 5 ]) may be harmful. It induces genetic and epigenetic changes and is more frequently associated with a range of physiological disturbances for the immune system, circulatory system, visual system, embryonic development, brain development, tumorigenesis and DNA molecules than the eruption rate inferred by the linear no-threshold (LNT) model [ 2 , 3 , 6 , 7 ]. These phenomena are known as ‘hypersensitivity (HRS),’ which means that harmful effects are greater than expected from those existing in the LNT model.…”

“…Only a few hypersensitive detection procedures can identify the DNA damage induced by radiation, ranging from doses of a few micrograys (μGy) to ~10 mGy [ 7 , 22 ]. In addition, only a few studies have investigated the effect of LDR on particular genes.…”

“…In addition, we also recovered the wings, including the mwh cells, to be able to further analyze the gene at the molecular level to determine the commonality or difference between the features of lesions caused by HDR and LDR. A report indicated that the genomic variations existing in Nature and those caused by LDR (<100 mGy) are hardly different [ 7 ]. In contrast, the variation rate caused by HDR (>0.15 Gy) is considerably higher than that existing in Nature [ 7 ].…”

“…A report indicated that the genomic variations existing in Nature and those caused by LDR (<100 mGy) are hardly different [ 7 ]. In contrast, the variation rate caused by HDR (>0.15 Gy) is considerably higher than that existing in Nature [ 7 ]. Moreover, the study indicated that the properties of mutations in the human hypoxanthine phosphoribosyltransferase ( HPRT ) gene are different [ 7 ].…”