Radiation-induced long-lived radicals which cause mutation and transformation

Koyama, Satoshi; Kodama, Seiji; Suzuki, Keiji; Matsumoto, Takurou; Miyazaki, Tetsuro; Watanabe, Masami

doi:10.1016/s0027-5107(98)00153-5

Cited by 137 publications

(55 citation statements)

References 23 publications

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“…It is, therefore, unlikely that medium would play a significant role in mediating the bystander mutagenic effect. Because DMSO is highly effective in scavenging hydroxyl radicals, our data would seem to rule out the role of this radical species, although other long-lived radicals not scavenged by DMSO could be involved (31).…”

Section: Discussionmentioning

confidence: 77%

“…The antioxidant DMSO has been shown to be an effective radical scavenger, particularly of hydroxyl radicals, and it can protect mammalian cells against the toxic and genotoxic effects of variety of agents such as ionizing radiation, asbestos fibers, and arsenic in which oxyradicals are known to mediate their biological effects (31,32,33). Table 1 shows that, in cells pretreated with 0.2% DMSO 24 hr before irradiation and maintained in it throughout the expression period, the bystander mutation frequency was like that in cells without DMSO treatment.…”

Section: Bystander Mutagenicity Of Alpha Particles Is Not Affected Bymentioning

confidence: 99%

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Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Zhou

Randers-Pehrson

Waldren

et al. 2000

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

428

281

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Ever since the discovery of X-rays was made by Rö ntgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear͞extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A L cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 M dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

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Section: Discussionmentioning

confidence: 77%

Section: Bystander Mutagenicity Of Alpha Particles Is Not Affected Bymentioning

confidence: 99%

Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Zhou

Randers-Pehrson

Waldren

et al. 2000

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

428

281

View full text Add to dashboard Cite

show abstract

“…However, there is evidence that, among confluent human fibroblast cultures, secretion of cytokines or other growth-promoting factors by irradiated cells leads to enhanced production of reactive oxygen species in bystander cells (6,7). These two observations among confluent cultures are not necessarily mutually exclusive because there is evidence that radiation induces long-lived organic radicals that persist for hours (34).…”

Section: Discussionmentioning

confidence: 99%

Radiation risk to low fluences of α particles may be greater than we thought

Zhou

Suzuki²,

Randers-Pehrson³

et al. 2001

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

200

132

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Based principally on the cancer incidence found in survivors of the atomic bombs dropped in Hiroshima and Nagasaki, the International Commission on Radiation Protection (ICRP) and the United States National Council on Radiation Protection and Measurements (NCRP) have recommended that estimates of cancer risk for low dose exposure be extrapolated from higher doses by using a linear, no-threshold model. This recommendation is based on the dogma that the DNA of the nucleus is the main target for radiationinduced genotoxicity and, as fewer cells are directly damaged, the deleterious effects of radiation proportionally decline. In this paper, we used a precision microbeam to target an exact fraction (either 100% or <20%) of the cells in a confluent population and irradiated their nuclei with exactly one ␣ particle each. We found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a confluent mammalian cell population with a single ␣ particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. This effect was significantly eliminated in cells pretreated with a 1 mM dose of octanol, which inhibits gap junction-mediated intercellular communication, or in cells carrying a dominant negative connexin 43 vector. The data imply that the relevant target for radiation mutagenesis is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimates for low dose, high linear-energy-transfer (LET) radiation exposure.

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“…Electron spin resonance studies have shown, however, that long-lived radicals with a period of half-lives ca. 20 hours may appear in cells after irradiation, even at room temperature (Koyama et al, 1998); if transferred to the surroundings, they may be the factors inducing DNA damage in non-irradiated cells. The long-lived secondary radicals are likely to be less active in damaging DNA than the extremely active primary radicals generated during irradiation time.…”

Section: The Mechanisms Of Radiation Induced Bystander Effectmentioning

confidence: 99%

“…The nature of these factors may be different and they have not been definitely defined. In addition to short-lived oxygen and nitrogen free radicals (Matsumoto et al, 2001, Azzam et al, 2002, long-lived radicals (Koyama et al, 1998), interleukin 8 (Narayanan et al, 1999), TGF- (Shao et al, 2008 a, b, Massague andChen, 2000) and other agents can be included. Potentially, bystander phenomenon could play an important role in the appearance of undesirable localized or systemic radiotherapeutic effects in tissues not included in the irradiation field.…”

mentioning

confidence: 99%

Intercellular Communication in Response to Radiation Induced Stress: Bystander Effects in Vitro and in Vivo and Their Possible Clinical Implications

Wideł¹

2011

Radioisotopes - Applications in Physical Sciences

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Radiation-induced long-lived radicals which cause mutation and transformation

Cited by 137 publications

References 23 publications

Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Radiation risk to low fluences of α particles may be greater than we thought

Intercellular Communication in Response to Radiation Induced Stress: Bystander Effects in Vitro and in Vivo and Their Possible Clinical Implications

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