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


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.
Ellender
M
M
Health Protection Agency, Radiation Protection Division, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon, UK. michele.ellender@hpa-rp.org.uk
Harrison
J D
JD
Kozlowski
R
R
Szłuińska
M
M
Bouffler
S D
SD
Cox
R
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004260:DNA Repair; D005333:Fetus / Q000528:radiation effects*; D017491:Genes, APC / Q000502:physiology*; D007414:Intestinal Neoplasms / Q000209:etiology*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis
C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins