Induction of Cell Killing, Micronuclei, and Mutation to 6-Thioguanine Resistance after Exposure to Low-Dose-Rate γ Rays and Tritiated Water in Cultured Mammalian Cells (L5178Y)

Ueno, Akihiko; Furuno-Fukushi, Ikuko; Matsudaira, Hiromichi

doi:10.2307/3575884

Cited by 42 publications

(19 citation statements)

References 12 publications

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“…1). Moreover, data on Hprt mutant frequencies in different somatic rodent cells [mouse LY cells (7)(8)(9)(10); Chinese hamster V79 cells, subline V79-S85 and other sublines (6), and the human TK6 lymphoblastoid cell line (3,12,14) corroborate this curvilinear relationship, which we approximated by using a second-order polynomial (parabolic) model (Fig. 1).…”

Section: Evidence For Inverse Dressupporting

confidence: 53%

“…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)(4)(5)(6)(7)(8)(9)(10)(11)(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.…”

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confidence: 99%

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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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Section: Evidence For Inverse Dressupporting

confidence: 53%

mentioning

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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“…A proper comparison of HTO RBE-values with different studies is nearly impossible due to the variety of in vitro experimental systems used (different cell types, biological endpoints, dose rates, irradiation setup, and reference radiation). Nevertheless, a methodological similar paper by Ueno et al report a similar, but slightly lower RBE-value of 1.5 for clonogenic cell survival data at 50% survival fraction after in vitro exposure of mouse lymphocytic leukemia (L5178Y) cells (Ueno et al 1982). In the context of our original study aim, any RBE higher than unity is by itself an important result, as it proves the basic proposition that very low energy beta particles deliver their dose with somewhat higher biological impact.…”

Section: Discussionsupporting

confidence: 64%

Radiobiological effects of tritiated water short-term exposure on V79 clonogenic cell survival

Siragusa

Fredericia

Jensen

et al. 2018

International Journal of Radiation Biology

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Purpose: We set out to improve the accuracy of absorbed dose calculations for in vitro measurements of the relative biological effectiveness (RBE) of tritiated water (HTO) for the clonogenic cell survival assay, also considering the influence of the end-of-track linear energy transfer (LET) of low-energy electrons. Materials and methods: The COmputation Of Local Electron Release (COOLER) program was adopted to investigate the cell geometry and the tritium full beta-decay spectrum impact on the S-values and subsequently on the RBE of HTO for clonogenic cell survival at similar high dose rates (HDR). Results: S-values for cells growing in suspension are usually comparable to those for adherent cells. RBEs calculated at the 10% survival fraction through the use of the average energy are almost similar to those obtained with the beta-spectrum. For adherent cells, an RBE of 1.6 was found when HTO cell survival curves were compared to acute c-ray exposures. Irrespective of the geometrical configuration, the RBE was 2.0 when the comparison was made with similar dose rates. Conclusions: These results underline the importance of irradiating at equal dose rates and cell culture conditions when measuring in vitro RBE-values. ARTICLE HISTORY

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“…Hence β rays are found to be more efficient in producing two lesions with a single ionizing track at low doses. Ueno et al (1982) has reported an RBE of 1.8 to 2.3 at low doses for micronuclei induction at a frequency of 50 or 25 micronuclei per 1000 cells; 1.8 at all doses for the induction of resistance to 6-thioguanine; 1.5 for 50% survival for cell killing, in L51785 mouse lymphocytic leukemia cells. In another study using blood lymphocytes Mill et al (1996) reported a low dose limiting RBE of 0.5 for beta particles.…”

Section: Resultsmentioning

confidence: 99%

Cytogenetic Effects of Tritiated Water (HTO) in Human Peripheral Blood Lymphocytesin vitro

Balakrishnan

Rao

2004

International Journal of Human Genetics

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The yield and distribution of unstable chromosome aberrations induced in human lymphocytes by tritiated water (HTO) has been measured. Tritiated water was mixed with heparinised blood in calculated amounts so as to give 0.1 Gy to 1.5 Gy, 30min and 2 hours. After culturing for 48 hrs, the dicentric yield was measured as a function of dose to the blood. Using a linear quadratic dose-effect relation to fit the experimental data, a significant linear contribution was found. The α, β values were found to be 8.25 + 0.4 x 10 -2 Gy -1 and 6.4 + 0.2 x10 -2 Gy -2 respectively. Micronuclei yield at low doses could be fitted to a linear equation Y= C + α D and indicates a á coefficient of 0.172 ±. 0.003. This value is found to be 2.18 and 2.8 times higher than those previously reported for X and gamma rays respectively. Hence β-rays are found to be more efficient in producing two lesions with single ionizing tracks at low doses.

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Induction of Cell Killing, Micronuclei, and Mutation to 6-Thioguanine Resistance after Exposure to Low-Dose-Rate γ Rays and Tritiated Water in Cultured Mammalian Cells (L5178Y)

Cited by 42 publications

References 12 publications

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

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

Radiobiological effects of tritiated water short-term exposure on V79 clonogenic cell survival

Cytogenetic Effects of Tritiated Water (HTO) in Human Peripheral Blood Lymphocytesin vitro

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