title: Effect of Age at Exposure on the Incidence of Lung and Mammary Cancer after Thoracic X-Ray Irradiation in Wistar Rats.
abstract: Epidemiology studies have shown that children are at greater overall risk of radiation-induced cancer, but the modifying effect of age at exposure in different tissues is heterogeneous. Early epidemiology findings of increased lung cancer risk with increasing age at the time of exposure have been dismissed, with suggestions that the trend is an artefact from a failure to adequately correct for the effects of tobacco smoking. Yet, differing models used in subsequent analyses have shown that the increased susceptibility with age, counter to the overall solid tumor trend, can either be confirmed or discounted depending on the model parameters used. In this study, we analyzed the induction of tumors in female Wistar rats exposed to increasing thoracic doses of X-ray as neonates, juveniles or young adults, to allow the effect of age at exposure in this early period to be observed in the absence of any interactions with smoking. Histology was used to compare tumor subtypes among groups, and genomic DNA copy number alterations in a number of tumors arising after irradiation at different ages were examined. Induction of lung cancers increased with radiation dose, with the frequency of early occurring lung adenomas greater in rats irradiated at older ages. At the highest dose, the rats irradiated at 5 or 15 weeks of age showed increased age-specific rates of lung adenocarcinomas in later life compared to those irradiated at 1 week of age. However, thoracic mammary gland tumors induced by the highest dose at the later ages significantly decreased the lifespan in these groups, reducing the number of rats at risk of radiation-induced lung adenocarcinoma. There was no induction of mammary tumors outside of the irradiated field. Lung adenocarcinomas showed widespread DNA copy number aberrations at the chromosome level, but the only recurrent lesions were intragenic Fhit deletions and losses on chromosome 4. The results presented here suggest that the risk of radiation-induced lung cancer after irradiation may not monotonically decrease with age, and demonstrate that increasing lung cancer risk with exposure age can be observed independent of corrections for smoking, and that mammary tumors may show a similar relationship with age.
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Iwata
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blyth
authors.affiliation: b   Fukushima Project Headquarters, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Doi
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Morioka
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Daino
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kakinuma
authors.affiliation: a   Department of Radiation Effects Research and.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000375:Aging / Q000528:radiation effects*; D000818:Animals; D056915:DNA Copy Number Variations / Q000528:radiation effects; D005260:Female; D015994:Incidence; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013909:Thorax / Q000528:radiation effects*; D014965:X-Rays / Q000009:adverse effects