Age-dependent susceptibility to azoxymethane-induced and spontaneous tumorigenesis in the Min/+ mouse.
We examined the age-dependent susceptibility to azoxymethane (AOM)-induced and spontaneous tumorigenesis in the Min/+ mouse, a murine FAP model. The colon carcinogen AOM was given to pups (weeks 1 and 2) and young adults (weeks 4 and 5). In the colon, AOM exposure of pups and young adults caused a 17-fold and 10-fold increase (p < 0.001) in the number of dysplastic aberrant crypt foci (ACF) compared with vehicle-treated controls, respectively; the pups were 1.7 times mores susceptible than young adults (p = 0.002). AOM-specific dysplastic ACF grew significantly faster (p < 0.001) in pups than in young adults. In the small intestine of AOM-exposed pups, the number of adenomas was increased 1.5-fold compared with controls (p < 0.001), while a similar exposure of young adults did not affect the tumorigenesis. Dysplastic ACF in the colon were morphologically equivalent with nascent adenomas in the small intestine. When comparing the size distributions of AOM-specific and spontaneous lesions the majority of the spontaneous lesions was apparently initiated before week 2. In conclusion, pups were more susceptible than young adults to AOM-induced and spontaneous tumorigenesis, and neonatal exposure was not as critical for AOM-induced tumorigenesis in the colon as in the small intestine.
Paulsen
Jan Erik
JE
Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403, Oslo, Norway. jan.erik.paulsen@fhi.no
Steffensen
Inger-Lise
IL
Namork
Ellen
E
Eide
Tor Jacob
TJ
Alexander
Jan
J
D000236:Adenoma / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000367:Age Factors; D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D003106:Colon / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011230:Precancerous Conditions / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000473:pathology
D002273:Carcinogens; D001397:Azoxymethane