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.