Monosodium glutamate-induced diabetic mice are susceptible to azoxymethane-induced colon tumorigenesis.
Obese people and diabetic patients are known to be high risk of colorectal cancer (CRC), suggesting need of a new preclinical animal model, by which to extensively study the diverse mechanisms, therapy and prevention. The present study aimed to determine whether experimental obese and diabetic mice produced by monosodium glutamate (MSG) treatment are susceptible to azoxymethane (AOM)-induced colon tumorigenesis using early biomarkers, aberrant crypts foci (ACF) and β-catenin-accumulated crypts (BCACs), of colorectal carcinogenesis. Male Crj:CD-1 (ICR) newborns were daily given four subcutaneous injections of MSG (2 mg/g body wt) to induce diabetes and obesity. They were then given four intraperitoneal injections of AOM (15 mg/kg body wt) or saline (0.1 ml saline/10 g body wt). Ten weeks after the last injection of AOM, the MSG-AOM mice had a significant increase in the multiplicity of BCAC (13.83 ± 7.44, P < 0.002), but not ACF (78.00 ± 11.20), when compare to the Saline-AOM mice (5.45 ± 1.86 of BCAC and 69.27 ± 8.06 of ACF). Serum biochemical profile of the MSG-treated mice with or without AOM showed hyperinsulinemia, hypercholesteremia and hyperglycemia. The mRNA expression of insulin-like growth factor-1 receptor (IGF-1R, P<0.01) was increased in the MSG-AOM mice, when compared with the mice given AOM alone. IGF-1R was immunohistochemically expressed in the BCAC, but not ACF, in the AOM-treated mice. Our findings suggest that the MSG mice are highly susceptible to AOM-induced colorectal carcinogenesis, suggesting potential utility of our MSG-AOM mice for further investigation of the possible underlying events that affect the positive association between obese/diabetes and CRC.
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. k-hata-sun@hhc.eisai.co.jp
Kazuya
K
Hata
Masaya
M
Kubota
Masahito
M
Shimizu
Hisataka
H
Moriwaki
Toshiya
T
Kuno
Takuji
T
Tanaka
Akira
A
Hara
Yoshinobu
Y
Hirose
D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006937:Hypercholesterolemia; D006943:Hyperglycemia; D006946:Hyperinsulinism; D007334:Insulin-Like Growth Factor I; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011230:Precancerous Conditions / Q000139:chemically induced; D012333:RNA, Messenger / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000494:pharmacology
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D001397:Azoxymethane; D012970:Sodium Glutamate