Unexpected Liver and Kidney Pathology in C57BL/6J Mice Fed a High-fat Diet and Given Azoxymethane to Induce Colon Cancer

被引:0
作者
Waggie, Kimberly S. [1 ]
Corulli, Lauren R. [2 ]
Cecil, Denise [2 ]
Rodmaker, Erin R. [2 ]
Walsh, Carissa [2 ]
Disis, Mary L. [2 ]
机构
[1] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA
[2] Univ Washington, Canc Vaccine Inst, Sch Med, Seattle, WA USA
关键词
MOUSE MODEL; OBESITY; METABOLISM;
D O I
10.30802/AALAS-CM-22-000040
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Multiple animal models have been developed to investigate the pathogenesis of colorectal cancer and to evaluate potential treatments. One model system uses azoxymethane, a metabolite of cycasin, alone and in conjunction with dextran sodium sulfate to induce colon cancer in rodents. Azoxymethane is metabolized by hepatic P450 enzymes and can also be eliminated through the kidneys. In this study, C57BL/6J mice were fed either standard or high-fat diet and then all mice received azoxymethane at 10 mg/kg body weight twice a week for 6 wk. Shortly after the end of treatment, high mortality occurred in mice in the high-fat diet group. Postmortem examination revealed hepatic and renal pathology in mice on both diets. Histologic changes in liver included hepatocytomegaly with nuclear pleomorphism and bile duct hyperplasia accompanied by mixed inflammatory-cell infiltrates. Changes in the kidneys ranged from basophilia of tubular epithelium to tubular atrophy. The results indicate that further optimization of this model is needed when feeding a high-fat diet and giving multiple azoxymethane doses to induce colon cancer in C57BL/6J mice.
引用
收藏
页码:330 / 335
页数:6
相关论文
共 32 条
[1]  
[Anonymous], 2011, Guide for the care and use of laboratory animals, V8th
[2]   Neurobiological characterization of an azoxymethane mouse model of acute liver failure [J].
Bélanger, M ;
Côté, J ;
Butterworth, RF .
NEUROCHEMISTRY INTERNATIONAL, 2006, 48 (6-7) :434-440
[3]   Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action [J].
Benkerroum, Noreddine .
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 2020, 17 (02)
[4]   Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults [J].
Bhaskaran, Krishnan ;
Douglas, Ian ;
Forbes, Harriet ;
dos-Santos-Silva, Isabel ;
Leon, David A. ;
Smeeth, Liam .
LANCET, 2014, 384 (9945) :755-765
[5]   Mouse models of colorectal cancer: Past, present and future perspectives [J].
Buertin, Florian ;
Mullins, Christina S. ;
Linnebacher, Michael .
WORLD JOURNAL OF GASTROENTEROLOGY, 2020, 26 (13) :1394-1426
[6]   The signal pathways in azoxymethane-induced colon cancer and preventive implications [J].
Chen, Jiezhong ;
Huang, Xu-Feng .
CANCER BIOLOGY & THERAPY, 2009, 8 (14) :1313-1317
[7]   Multi-Epitope-Based Vaccines for Colon Cancer Treatment and Prevention [J].
Corulli, Lauren R. ;
Cecil, Denise L. ;
Gad, Ekram ;
Koehnlein, Marlese ;
Coveler, Andrew L. ;
Childs, Jennifer S. ;
Lubet, Ronald A. ;
Disis, Mary L. .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[8]   DIFFERENTIAL SUSCEPTIBILITY OF 3 SUBLINES OF C57BL-6 MICE TO THE INDUCTION OF COLORECTAL TUMORS BY 1,2-DIMETHYL-HYDRAZINE [J].
DIWAN, BA ;
BLACKMAN, KE .
CANCER LETTERS, 1980, 9 (02) :111-115
[9]   Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure [J].
Doering, CB ;
Josephson, CD ;
Craddock, HN ;
Lollar, P .
BLOOD, 2002, 100 (01) :143-147
[10]   Inflammatory Links Between High Fat Diets and Diseases [J].
Duan, Yehui ;
Zeng, Liming ;
Zheng, Changbing ;
Song, Bo ;
Li, Fengna ;
Kong, Xiangfeng ;
Xu, Kang .
FRONTIERS IN IMMUNOLOGY, 2018, 9