Molecular analysis of mutations in T-lymphocytes from experienced Soviet cosmonauts

Khaidakov, Magomed; Young, D. F.; Erfle, Heather; Mortimer, A.J.; Voronkov, Yu. I.; Glickman, Barry W.

doi:10.1002/(sici)1098-2280(1997)30:1<21::aid-em4>3.0.co;2-f

Cited by 18 publications

(3 citation statements)

References 49 publications

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“…Such radiations are capable of inducing chromosome aberrations and gene mutations after long-term space flights (Khaidakov et al, 1997;Yang et al, 1997;Cutinotta et al, 2008). Many researchers have investigated the biological effects of iron ions using chromosomal aberrations as a biomarker for radiobiological effects (Dini et al, 2005;Durante et al, 2005;Lee et al, 2005;Hada et al, 2007;Pignalosa et al, 2008), however only limited reports have been available about mutation induction in normal human cells induced by iron ions.…”

Section: Introductionsupporting

confidence: 69%

The Influence of Mutation Induction in Normal Human Fibroblasts Irradiated with X Rays and Iron Ions

Tsuruoka¹,

Suzuki²,

Furusawa³

et al. 2009

Biol. Sci. Space

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We investigated the influence of mutation i n d u c t i o n o n t h e hy p ox a n t h i n e g u a n i n e phosphoribosyltransferase (hprt ) locus in normal human fibroblasts irradiated with X rays or accelerated iron ions with LET ranging from 200 to 400 keV/µm. The relative biological effectiveness (RBE) of the mutation frequency per total number of surviving cells for iron ions with comparatively lower LET values (200 and 260 keV/µm) in this study was higher than 1, and the RBE for the 300 keV/µm, 350 keV/ µm and 400 keV/µm ions was nearly 1. These results indicated that the mutation induction for iron ions decreased with increasing LET, and these of high-LET regions (over 300 keV/µm) and X rays were similar. The deletion spectrum of exons in hprt locus for X rays and 260 keV/ µm-iron ions were analyzed using multiplex polymerase chain reaction (PCR). About 70% of mutant induced by iron ions showed deletion of the entire exons (total deletion), while mutant induced by X rays showed partial deletion, which one or more exons are missing, of about 70%. The results indicated that iron-ion induced mutants sustained severer damage than X-ray induced mutants even if the doseresponse curves for mutation induction were similar between X rays and iron ions.

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Section: Introductionsupporting

confidence: 69%

The Influence of Mutation Induction in Normal Human Fibroblasts Irradiated with X Rays and Iron Ions

Tsuruoka¹,

Suzuki²,

Furusawa³

et al. 2009

Biol. Sci. Space

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“…However, mutant frequencies were elevated in lymphocytes of humans exposed to low doses of ionizing radiation at low and͞or very low DRs (22)(23)(24)(25), relative to high DRs. There may, therefore, be an inverse effect at very low DRs, but a synergistic effect with chemical mutagens cannot be ruled out (26,27).…”

Section: Evidence For Inverse Dresmentioning

confidence: 99%

Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates

Vilenchik

Knudson

2000

Proc. Natl. Acad. Sci. U.S.A.

136

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The mutagenic effect of low linear energy transfer ionizing radiation is reduced for a given dose as the dose rate (DR) is reduced to a low level, a phenomenon known as the direct DR effect. Our reanalysis of published data shows that for both somatic and germ-line mutations there is an opposite, inverse DR effect, with reduction from low to very low DR, the overall dependence of induced mutations being parabolically related to DR, with a minimum in the range of 0.1 to 1.0 cGy͞min (rule 1). This general pattern can be attributed to an optimal induction of error-free DNA repair in a DR region of minimal mutability (MMDR region). The diminished activation of repair at very low DRs may reflect a low ratio of induced (''signal'') to spontaneous background DNA damage (''noise''). Because two common DNA lesions, 8-oxoguanine and thymine glycol, were already known to activate repair in irradiated mammalian cells, we estimated how their rates of production are altered upon radiation exposure in the MMDR region. For these and other abundant lesions (abasic sites and single-strand breaks), the DNA damage rate increment in the MMDR region is in the range of 10% to 100% (rule 2). These estimates suggest a genetically programmed optimatization of response to radiation in the MMDR region.T he dose-rate effect (DRE) on mutation has important implications for genetics and radioprotection. The risk of genetic effects of ionizing radiation for both somatic and germ cells decreases with reduction of dose rate (DR). This phenomenon is called the direct DRE (reviewed in refs. 1 and 2). But some somatic cell lines show inverse DREs, with higher sensitivity to mutation induced by low linear energy transfer (LET) radiation (3-12) or to oncogenic transformation induced by fission neutrons (2) at very low DRs than at low DRs. However, some investigators have reported a direct DRE (1, 12) or no DRE (13,14), at very low DRs of continuous (13) or fractionated (14) low LET radiation. With respect to mutational DREs in germ cells, Lyon and coworkers (15) have suggested a similar inverse effect at very low DRs, whereas Russell and coworkers (16) concluded that their data did not confirm such an effect. The general view is that germ-line mutations do not show an inverse DRE (reviewed in ref. 1). Here we reanalyze these data, together with recent low LET data on DREs, and conclude that there is indeed a general pattern of inverse effects at very low DRs for both somatic and germ cells. Evidence for Inverse DREsSomatic HPRT Mutation in Mammalian Cells in Vitro. Although there are data on other genetic DREs than HPRT mutation in somatic mammalian cells (for review see refs. 1, 5, and 17), we limited our analysis to HPRT mutations because they have been the most studied. For the most part, the data were obtained by using low LET radiation, i.e., x-rays and ␥-rays. The low DR somatic mutation data that we plot in Fig. 1 all were evaluated and reviewed in at least four reviews published in the 1990s (1, 4-6) with one exception for a radiosensitive mu...

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“…Under this condition, cells were more prone to develop single nucleotide variants (SNV), including radiation-associated SNVs. A similar mutagenic effect would have detrimental consequences on human cells exposed to space radiation, where however an increase in mutant frequency at HPRT gene has been reported in cosmonauts [105]. It is also therefore expected that genes responsible for the carcinogenic process might undergo mutation under the combined action of radiation and microgravity.…”

Section: Genetic and Epigenetic Changes Associated With Radiation Carcinogenesis Riskmentioning

confidence: 84%

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Beheshti

McDonald

Hada

et al. 2021

IJMS

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The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

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Molecular analysis of mutations in T-lymphocytes from experienced Soviet cosmonauts

Cited by 18 publications

References 49 publications

The Influence of Mutation Induction in Normal Human Fibroblasts Irradiated with X Rays and Iron Ions

The Influence of Mutation Induction in Normal Human Fibroblasts Irradiated with X Rays and Iron Ions

Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

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