Gastroenterology

Gastroenterology

Volume 114, Issue 5, May 1998, Pages 873-877
Gastroenterology

Rapid Communication
Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli Min mouse model with aspirin,☆☆

https://doi.org/10.1016/S0016-5085(98)70305-1Get rights and content

Abstract

Background & Aims: Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Epidemiological and experimental data indicate that regular use of aspirin reduces colon cancer risk. This study was designed to determine if aspirin would significantly inhibit gastrointestinal tumor formation in a mouse model of familial adenomatous polyposis. Methods: Six-week-old male and female C57BL/6J +/+ (control) and C57BL/6J ApcMin/+ (Min) mice were fed either a control AIN-76A diet or one supplemented with 250 or 500 parts per million (ppm) aspirin (n = 6 per group) for 7 weeks. Results: All of the Min mice, but no control mice, developed gastrointestinal tumors. Aspirin significantly reduced tumor multiplicity (number of tumors per mouse) in the small intestine, but not the colon, from an average of 35.8 tumors per mouse (control diet) to 16 and 18.5 tumors per mouse with 250 and 500 ppm aspirin, respectively. Total tumor load (sum of tumor diameters per mouse) was also significantly reduced, from 93.2 mm in total diameter to 40.4 and 45.0 mm with 250 and 500 ppm aspirin, respectively. Results were not significantly different because of sex or aspirin dose. Conclusions: High doses of aspirin are effective chemopreventive agents in a mouse model of spontaneous intestinal tumor formation.

GASTROENTEROLOGY 1998;114:873-877

Section snippets

Animals

Nine male and 9 female C57BL/6J +/+ (control) mice and 9 male and 9 female C57BL/6J Min mice were purchased from Jackson Laboratories (Bar Harbor, ME) at 5 weeks of age. Upon receipt, male Min mice weighed significantly less than male control mice (22.4 ± 0.3 vs. 23.6 ± 0.3 g, mean ± SEM, respectively; P = 0.02), but there was no significant difference in initial body weight between Min and control females (17.3 ± 0.2 vs. 18.3 ± 0.4 g, respectively; P = 0.07). Mice had free access to food and

Results

At the end of 7 weeks, all Min mice had developed spontaneous intestinal tumors, whereas none of the control C57BL/6J mice had tumors. Histological examination of H&E-stained tumor sections showed that two small intestinal tumors were locally invasive through the muscularis mucosa, whereas the remaining tumors were adenomas.

As shown in Table 1, aspirin added to the diet at both 250 and 500 ppm significantly (P < 0.05) reduced tumor multiplicity (number of tumors per mouse) in the proximal,

Discussion

Human epidemiological data and experiments utilizing carcinogen-induced rodent models of colon cancer have provided ample evidence indicating that aspirin is an important colon cancer chemopreventive agent.1 Our data show for the first time that aspirin reduces the formation of spontaneous intestinal tumors in mice with a genetic predisposition to develop intestinal tumors, thus providing additional evidence for regular aspirin use as an effective chemopreventive strategy. In the present study,

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    Address requests for reprints to: Makau Lee, M.D., Ph.D, Department of Medicine/Division of Gastroenterology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7878. e-mail: [email protected]; fax: (210) 567-1976.

    ☆☆

    Supported in part by the San Antonio Cancer Institute and by National Cancer Institute Research Center Award P30 CA 54174. Makau Lee is a recipient of the Paul Beeson Physician Faculty Scholars in Aging Research Award.

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