Genomic instability after targeted irradiation of human lymphocytes

Evidence for inter-individual differences under bystander conditions

Munira A. Kadhim, Ryonfa Lee, Stephen Moore, Denise A. Macdonald, Kim L. Chapman, Gaurang Patel, Kevin M. Prise

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

Original languageEnglish (US)
Pages (from-to)91-94
Number of pages4
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume688
Issue number1-2
DOIs
StatePublished - Jun 2010
Externally publishedYes

Fingerprint

Genomic Instability
Individuality
Lymphocytes
Radiation
Bystander Effect
Chromosome Aberrations
Genotype
Linear Energy Transfer
Environmental Exposure
Genetic Predisposition to Disease
Cell Nucleus
Immobilization
Population
Carcinogenesis
Phenotype
Health

Keywords

  • Bystander effects
  • Genomic instability
  • Human lymphocytes
  • Individual variation
  • Microbeam
  • Radiosensitivity

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Genomic instability after targeted irradiation of human lymphocytes : Evidence for inter-individual differences under bystander conditions. / Kadhim, Munira A.; Lee, Ryonfa; Moore, Stephen; Macdonald, Denise A.; Chapman, Kim L.; Patel, Gaurang; Prise, Kevin M.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 688, No. 1-2, 06.2010, p. 91-94.

Research output: Contribution to journalArticle

Kadhim, Munira A. ; Lee, Ryonfa ; Moore, Stephen ; Macdonald, Denise A. ; Chapman, Kim L. ; Patel, Gaurang ; Prise, Kevin M. / Genomic instability after targeted irradiation of human lymphocytes : Evidence for inter-individual differences under bystander conditions. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2010 ; Vol. 688, No. 1-2. pp. 91-94.
@article{2ebcf41f171042f7a800a8b5bee908d0,
title = "Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions",
abstract = "Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15{\%} of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.",
keywords = "Bystander effects, Genomic instability, Human lymphocytes, Individual variation, Microbeam, Radiosensitivity",
author = "Kadhim, {Munira A.} and Ryonfa Lee and Stephen Moore and Macdonald, {Denise A.} and Chapman, {Kim L.} and Gaurang Patel and Prise, {Kevin M.}",
year = "2010",
month = "6",
doi = "10.1016/j.mrfmmm.2010.03.013",
language = "English (US)",
volume = "688",
pages = "91--94",
journal = "Mutation Research",
issn = "1386-1964",
publisher = "Elsevier BV",
number = "1-2",

}

TY - JOUR

T1 - Genomic instability after targeted irradiation of human lymphocytes

T2 - Evidence for inter-individual differences under bystander conditions

AU - Kadhim, Munira A.

AU - Lee, Ryonfa

AU - Moore, Stephen

AU - Macdonald, Denise A.

AU - Chapman, Kim L.

AU - Patel, Gaurang

AU - Prise, Kevin M.

PY - 2010/6

Y1 - 2010/6

N2 - Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

AB - Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

KW - Bystander effects

KW - Genomic instability

KW - Human lymphocytes

KW - Individual variation

KW - Microbeam

KW - Radiosensitivity

UR - http://www.scopus.com/inward/record.url?scp=77952882545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952882545&partnerID=8YFLogxK

U2 - 10.1016/j.mrfmmm.2010.03.013

DO - 10.1016/j.mrfmmm.2010.03.013

M3 - Article

VL - 688

SP - 91

EP - 94

JO - Mutation Research

JF - Mutation Research

SN - 1386-1964

IS - 1-2

ER -