title: Chromosome analysis in childhood cancer survivors and their offspring--no evidence for radiotherapy-induced persistent genomic instability.
abstract: Suggestions that the induction of genomic instability could play a role in radiation-induced carcinogenesis and heritable disease prompted the investigation of chromosome instability in relation to radiotherapy for childhood cancer. Chromosome analysis of peripheral blood lymphocytes at their first in vitro division was undertaken on 25 adult survivors of childhood cancer treated with radiation, 26 partners who acted as the non-irradiated control group and 43 offspring. A statistically significant increase in the frequency of dicentrics in the cancer survivor group compared with the partner control group was attributed to the residual effect of past radiation therapy. However, chromatid aberrations plus chromosome gaps, the aberrations most associated with persistent instability, were not increased. Therefore, there was no evidence that irradiation of the bone marrow had resulted in instability being transmitted to descendant cells. Frequencies of all aberration categories were significantly lower in the offspring group, compared to the partner group, apart from dicentrics for which the decrease did not reach statistical significance. The lower frequencies in the offspring provide no indication of transmissible instability being passed through the germline to the somatic cells of the offspring. Thus, in this study, genomic instability was not associated with radiotherapy in those who had received such treatment, nor was it found to be a transgenerational radiation effect.
authors.affiliation: Westlakes Research Institute, Moor Row, Cumbria CA24 3JY, UK. Janet.Tawn@westlakes.ac.uk
authors.forename: E Janet
authors.initials: EJ
authors.lastname: Tawn
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Whitehouse
authors.forename: Jeanette F
authors.initials: JF
authors.lastname: Winther
authors.forename: Gillian B
authors.initials: GB
authors.lastname: Curwen
authors.forename: Gwen S
authors.initials: GS
authors.lastname: Rees
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Jørgen H
authors.initials: JH
authors.lastname: Olsen
authors.forename: Per
authors.initials: P
authors.lastname: Guldberg
authors.forename: Catherine
authors.initials: C
authors.lastname: Rechnitzer
authors.forename: Henrik
authors.initials: H
authors.lastname: Schrøder
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D020732:Cytogenetic Analysis; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000097:blood / Q000528:radiation effects; D008297:Male; D009369:Neoplasms / Q000532:radiotherapy*; D011874:Radiometry; D011878:Radiotherapy / Q000009:adverse effects*; D017741:Survivors