In utero and neonatal sensitivity of Apc^Min/+ mice to radiation-induced intestinal neoplasia

Abstract

Purpose: To assess the sensitivity of Apc^Min/+ 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 Apc^Min/+ 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 Apc^Min/+ 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 Apc^Min/+ 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.

Keywords:

• Intestinal neoplasia
• Min mouse
• x-irradiation
• In utero
• neonates