Intestinal tumours induced in ApcMin/+ mice by X-rays and neutrons

• Published in: International journal of radiation biology 2011-04, Vol.87 (4), p.385-399
• Main Authors: Ellender, Michele, Harrison, John D., Meijne, Emmy, Huiskamp, Rene, Kozlowski, Ryszard E., Haines, Jackie W., Edwards, Alan A., Ainsbury, Elizabeth A., Moody, John C., Bouffler, Simon D., Cox, Roger
• Format: Article
• Language: English
• Subjects: intestinal neoplasia; Min mouse; neutron irradiation; X-irradiation
• ISSN: 0955-3002; 1362-3095
• DOI: 10.3109/09553002.2011.542542

Purpose: To compare the development of intestinal adenomas following neutron and X-ray exposure of ApcMin/+ 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.