Experimental model of upper intestinal adenocarcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine in C57BL/6 mice.
The purpose of this study was to develop a model of gastrointestinal carcinogenesis using C57BL/6 mice. Treatment regimens consisted of one control group and 2 groups which received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water: 50 micrograms/ml x 52 weeks and 100 micrograms/ml x 27 weeks. In addition, 2 protocols using adjuvant agents intended to increase tumor formation were used: MNNG (100 micrograms/ml) x 27 weeks + 0.2% taurocholic acid added to the diet from weeks 13-52, and MNNG (50 micrograms/ml) x 33 weeks+caerulein (10 micrograms/kg) subcutaneously 3 times/week from weeks 21-52. High-grade dysplasia was observed in the duodenum of 1/13 mice treated with MNNG (50 micrograms/ml). The combination of the latter and caerulein did not augment tumorigenesis. Mice treated with MNNG (100 micrograms/ml) frequently developed neoplasia in the duodenum and upper jejunum. Foci of low-grade and high-grade dysplasia alone were found in 3/12 (25%) mice; and intramucosal and invasive adenocarcinoma were found in 7/12 (58.3%) mice. The addition of taurocholic acid significantly increased the number and histological stages of the tumors (adenocarcinoma occurred in 100%, P = 0.03) and decreased the time for tumor formation.
Ho
S B
SB
Department of Medicine, University of Minnesota, Minneapolis, USA.
Lyftogt
C T
CT
Shekels
L L
LL
Niehans
G A
GA
D000230:Adenocarcinoma / Q000139:chemically induced*; D000284:Administration, Oral; D000818:Animals; D002108:Ceruletide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced*; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D013656:Taurocholic Acid / Q000008:administration & dosage
D008769:Methylnitronitrosoguanidine; D013656:Taurocholic Acid; D002108:Ceruletide