DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models.

DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Research Abstract Details 

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DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Abstract Text:

Olga A Sedelnikova,Asako Nakamura,Olga Kovalchuk,Igor Koturbash,Stephen A Mitchell,Stephen A Marino,David J Brenner,William M Bonner,

The "radiation-induced bystander effect," in which irradiated cells can induce genomic instability in unirradiated neighboring cells, has important implications for cancer radiotherapy and diagnostic radiology as well as for human health in general. Although the mechanisms of this effect remain to be elucidated, we reported previously that DNA double-strand breaks (DSBs), directly measured by gamma-H2AX focus formation assay, are induced in bystander cultured cells. To overcome the deficiencies of cultured cell studies, we examined alpha-particle microbeam irradiation-induced bystander effects in human tissue models, which preserve the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. In marked contrast to DNA DSB dynamics in irradiated cells, in which maximal DSB formation is seen 30 min after irradiation, the incidence of DSBs in bystander cells reached a maximum by 12 to 48 h after irradiation, gradually decreasing over the 7-day time course. At the maxima, 40% to 60% of bystander cells were affected, a 4- to 6-fold increase over controls. These increases in bystander DSB formation were followed by increased levels of apoptosis and micronucleus formation, by loss of nuclear DNA methylation, and by an increased fraction of senescent cells. These findings show the involvement of DNA DSBs in tissue bystander responses and support the notion that bystander DNA DSBs are precursors to widespread downstream effects in human tissues. Bystander cells exhibiting postirradiation signs of genomic instability may be more prone than unaffected cells to become cancerous. Thus, this study points to the importance of considering the indirect biological effects of radiation in cancer risk assessment.

DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Publishing Authors By Initials

OA Sedelnikova,A Nakamura,O Kovalchuk,I Koturbash,SA Mitchell,SA Marino,DJ Brenner,WM Bonner,

For similar respiratory system: trachea research abstracts see: respiratory system: trachea research

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DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 4295-302

Journal Abbreviation:

ISSN: 0008-5472

DAY: 1

MONTH: May

YEAR: 2007

DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Keywords Mesh Terms:

KEYWORDS: Trachea

MESH TERMS: cytology

Chemical & Substance for Abstract: DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models.

AFFILIATION: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. sedelnio@mail.nih.gov

Country: United States

AGENCY: United States NIBIB

GRANT: P41 EB002033-09

ACRONYM: EB

MEDLINETA: Cancer Res

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