In utero and neonatal sensitivity of ApcMin/+ mice to radiation-induced intestinal neoplasia

Michele Ellender*, John Harrison, R. Kozlowski, M. Szłuińska, Simon Bouffler, R. Cox

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Purpose: To assess the sensitivity of ApcMin/+ mice (adenomatous polyposis coli Apc, multiple intestinal neoplasia, Min) to the development of intestinal adenomas after x-irradiation in utero, as neonates, or as young adults. Materials and methods: CHB6 ApcMin/+ mice were exposed to an acute dose of 2 Gy x-rays either in utero on day 7 or 14 post-conception, as 2-day or 10-day neonates or as 35-day young adults. Tumour identification and counting was performed 200-214 days later. Results: Irradiation as 10-day-old neonates resulted in a significantly greater overall tumour incidence (average of about 130 tumours per animal) than irradiation as 35-day-old young adults (about 70 tumours). Irradiation as 2-day-old neonates resulted in an intermediate incidence (about 85 tumours). In contrast, the greatest tumour incidence observed after in utero irradiation of ApcMin/+ mice, of about 44 tumours per animal after 2 Gy irradiation at 14 days post-conception, was significantly lower than the incidence in irradiated adults. Tumour incidences after irradiation as 7-day embryos was not significantly raised above numbers in unirradiated controls (about 30 tumours). These tumour numbers include cystic crypts, largely radiation-induced, which were classed as early stage microadenomas on the basis of loss of wild-type Apc+ and expression of beta-catenin. Conclusions: The sensitivity of ApcMin/+ mice to the induction of intestinal tumours by radiation was shown to be in the order: 10 d neonates >2 d neonates >35 d young adults > 14 d fetus >7 d embryo.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalInternational Journal of Radiation Biology
Volume82
Issue number3
DOIs
Publication statusPublished - 1 Mar 2006

Bibliographical note

Funding Information:
This work was supported in part by the UK Department of Health (Contract Number: RRX62) and by the European Commission (RISC-RAD project: FI6R-CT-2003-508842). The authors thank Kevin Whitehill and Rachel Bartram for animal care, Emma Davies for laboratory assistance, Margaret Coster and Helen Pottinger for genotyping the mice and Paul Bonner of the Medical Research Council Radiation and Genome Stability Unit, Harwell, Didcot, Oxon, OX11 0RD, UK for performing the x-ray exposures.

Keywords

  • In utero
  • Intestinal neoplasia
  • Min mouse
  • Neonates
  • X-irradiation

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