In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

Koturbash, Igor; Loree, Jonathan M.; Kutanzi, Kristy; Koganow, Clayton; Pogribny, Igor P.; Kovalchuk, Olga

doi:10.1016/j.ijrobp.2007.09.039

Cited by 105 publications

(74 citation statements)

References 54 publications

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“…The same shielding was used in the published studies on the bystander effect in mouse skin and in mouse and rat spleen. [14][15][16] We also considered the fact that even though the shielding of the animal body is complete, the X-rays can be reflected as they pass through the tissue, thus forming a small 'scatter' dose in the protected tissue. 16 To check if a possible small scatter dose could contribute to the generation of bystander effects in testes, we exposed a separate cohort of animals to a scatter dose of ~0.0012 Gy calculated according to the Monte Carlo simulation and directly measured by RAD-CHECK TM .…”

Section: Resultsmentioning

confidence: 99%

“…16 To check if a possible small scatter dose could contribute to the generation of bystander effects in testes, we exposed a separate cohort of animals to a scatter dose of ~0.0012 Gy calculated according to the Monte Carlo simulation and directly measured by RAD-CHECK TM . [14][15][16] Sham treated animals served as a control group.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous studies, we showed a pronounced induction of DNA damage and particularly DNA double-strand breaks (DSBs) in the bystander cells and tissues. 14,16,17 In the light of these considerations, we studied if the cranial X-ray exposure induces DNA damage in the shielded whole testes tissue of control, cranialexposed and scatter-exposed animals one week after irradiation. DNA strand breaks were measured using a modification of the random oligonucleotide primed synthesis (ROPS) assay.…”

Section: Resultsmentioning

confidence: 99%

“…It has been shown previously that the accumulation of DNA damage is accompanied by the loss of DNA methylation, [24][25][26] and the bystander effects X-irradiation may be epigenetically mediated. [11][12][13][14][15]27 DNA methylation is an important epigenetic mechanism that safeguards genome stability of the cells, regulates gene expression and chromatin structure. [28][29][30] The altered DNA methylation has deleterious consequences for the sperm cells.…”

Section: Resultsmentioning

confidence: 99%

“…6,13 Recent studies have shown that bystander effects also operate in vivo, and that body part or cranial irradiation may exert deleterious changes in the distant protected somatic tissues. [14][15][16] However, the potential of distant bystander damage to the germline has never been studied.…”

Section: Introductionmentioning

confidence: 99%

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Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring

Tamminga

Koturbash²,

Baker³

et al. 2008

Cell Cycle

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It is now well accepted that parental whole body irradiation causes transgenerational genome and epigenome instability in the offspring. The majority of human exposures to radiation, such as therapeutic and diagnostic irradiation, are localized and focused. The potential of localized body-part exposures to affect the germline and thus induce deleterious changes in the progeny has not been studied. To investigate whether or not the paternal cranial irradiation can exert deleterious changes in the protected germline, we studied the accumulation of DNA damage in the shielded testes tissue. Here we report that the localized paternal cranial irradiation results in a significant accumulation of unrepaired DNA lesions in sperm cells and leads to a profound epigenetic dysregulation in the unexposed progeny conceived a week after paternal exposure.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring

Tamminga

Koturbash²,

Baker³

et al. 2008

Cell Cycle

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The Bystander Effect in Targeted Radiotherapy

Mothersill¹,

Seymour²

2010

Monoclonal Antibody and Peptide‐Targeted Radiotherapy of Cancer

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Radiation‐induced bystander effects in vivo are epigenetically regulated in a tissue‐specific manner

Ilnytskyy

Koturbash

Kovalchuk

2008

Environ and Mol Mutagen

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113

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Exposure of animal body parts to ionizing radiation (IR) can lead to molecular changes in distant shielded “bystander” tissues and organs. Nevertheless, tissue specificity of bystander responses within the same organism has not been examined in detail. Studies on in vivo bystander effect conducted so far analyzed changes induced by single‐dose exposure. The potential of fractionated irradiation to induce bystander effects in vivo has never been studied. We analyzed changes in global DNA methylation and microRNAome in skin and spleen of animals subjected to single‐dose (acute or fractionated) whole‐body or cranial exposure to 0.5 Gy of X‐rays. We found that IR‐induced DNA methylation changes in bystander spleen and skin were distinct. Acute radiation exposure resulted in a significant loss of global DNA methylation in the exposed and bystander spleen 6 hr, 96 hr, and 14 days after irradiation. Fractionated irradiation led to hypomethylation in bystander spleen 6 hr after whole‐body exposure, and 6 hr, 96 hr, and 14 days after cranial irradiation. Contrarily, changes in the skin of the same animals were seen only 6 hr after acute whole‐body and head exposure. DNA hypomethylation observed in spleen was paralleled by a reduction of methyl‐binding protein MeCP2 expression. Irradiation also induced tissue‐specific microRNAome alterations in skin and spleen. For the first time, we have shown that IR‐induced epigenetic bystander effects that occur in the same organism are triggered by both acute and fractionated exposure and are very distinct in different bystander organs. Future studies are clearly needed to address organismal and carcinogenic repercussions of those changes. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.

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In Vivo Bystander Effect: Cranial X-Irradiation Leads to Elevated DNA Damage, Altered Cellular Proliferation and Apoptosis, and Increased p53 Levels in Shielded Spleen

Cited by 105 publications

References 54 publications

Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring

Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring

The Bystander Effect in Targeted Radiotherapy

Radiation‐induced bystander effects in vivo are epigenetically regulated in a tissue‐specific manner

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