Intestinal tumours induced in Apc^Min/+ mice by X-rays and neutrons

Abstract

Purpose: To compare the development of intestinal adenomas following neutron and X-ray exposure of Apc^Min/+ mice (Apc – adenomatous polyposis coli; Min – multiple intestinal neoplasia).

Materials and methods: Adult mice were exposed to acute doses of X-rays or fission neutrons. Tumour counting was undertaken 200 days later and samples were taken for Loss of Heterozygosity (LOH) analysis.

Results: Tumour numbers (adenomas and microadenomas) increased by 1.4-fold, 1.7-fold, 2.7-fold and 9-fold, after 0.5, 1, 2 and 5 Gy X-rays, respectively, and by 2.4-fold and 5.7-fold, after 0.5 and 1 Gy fission neutrons, respectively. LOH analysis of tumours from neutron-exposed mice showed that 63% had lost Apc and 90% (cf. 53% in controls) had lost D18mit84, a marker for Epb4.1l4a/NBL4 (erythrocyte protein band 4.1-like 4a/novel band 4.1-like 4), known to be involved in the Wnt (wingless-related mouse mammary tumour virus integration site) pathway. Some tumours from neutron-exposed mice appeared to have homozygous loss of some chromosomal markers.

Conclusions: X-ray or fission neutron irradiation results in strongly enhanced tumour multiplicities. Comparison of tumour yields indicated a low Relative Biological Effectiveness of around 2–8 for fission neutrons compared with X-rays. LOH in intestinal tumours from neutron-exposed mice appeared to be more complex than previously reported for tumours from X-irradiated mice.

Keywords:

• intestinal neoplasia
• Min mouse
• X-irradiation
• neutron irradiation

Acknowledgements

This work was supported in part by the European Commission (contract grant numbers F14P-CT95-008 and the RISC-RAD project: FI6R-CT-2003–508842). The authors thank Kevin Whitehill and Rachel Bartram for animal care, Sylvia Spanjer and Emma Davies for laboratory assistance, Margaret Coster and Helen Pottinger for genotyping the mice and Paul Bonner of the Medical Research Council, Harwell, Didcot, Oxon, OX11 0RD, UK for performing the x-ray exposures.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.