Abstract

Colon cancer is responsible for a high percentage of cancer deaths in developing countries, and there is convincing epidemiological evidence that meat protein and fat in the diet increase the incidence of this form of cancer. An animal tumor model which has been used by many investigators interested in colon cancer is the 1,2-dimethylhydrazine (DMH)-rat or DMH-mouse tumor model. In previous work done in this laboratory the DMH-BALB/c mouse tumor model was used to compare the production of colon tumors in mice fed a diet using non-fat powdered milk as a source of protein with those in mice fed beef as protein source. In contrast with epidemiological findings (and also contrary to results with other tumor models where milk was found to restrict tumor growth), colon tumor incidence was much greater in the milk-fed mice than in the beef-fed mice. Since dietary fiber studies in the DMH-mouse tumor model in another laboratory had also produced results contrary to human epidemiological findings, it was suggested that it would be well to investigate the DMH-rat tumor model with the hypothesis that it would more closely mimic the human and the epidemiological findings in humans. In order to investigate this possibility the current investigation was undertaken.

One hundred 5-week-old male Sprague-Dawley rats were divided into four diet groups: 1) a low (5%) fat, low (11%) protein diet with non-fat powdered milk as protein source, 2) a diet composed similarly except that beef was used as protein source and beef tallow replaced corn oil, 3) a control diet similar to the first diet except that casein (no lactose) was substituted for milk, and 4) the standard recommended balanced diet for rats and mice (AIN-76A) which was similar to the third diet except that protein level was moderate (about 19%). At 12 weeks of age, and for each of the 9 weeks following, each rat received an injection of DHM (10 mg/kg of body wt.). The 82 rats which were still alive were euthanized and necropsied at 52 weeks of age. Spleens and colons were removed and weighed, tumor counts were made and the tumors prepared for pathological examination. Spleen cells were removed and assays for cell-mediated immunity were performed: lymphocyte transformation test (LTT) with phytohemagglutinin (PHA) and concanavalin A (Con A) as mitogens, as well as assays for natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activity.

The percentages of rats with tumors found at euthanization were: 1) low milk-fed rats - 44%, 2) low beef-fed rats - 79%, 3) low casein—fed rats - 64%, and 4) moderate casein fed rats - 50%. Most of the tumors were in the colons. As in the previous study, colons were significantly heavier in rats fed the diet containing lactose, but this did not appear to enhance colon tumor growth. There was too much variation in the NK and CTL test results for any significance to be noted. In the LTT test, rats without tumors were more apt to have high cell-mediated immunity than those with tumors. Also, with both mitogens, rats fed the AIN-76A control has the highest cell-mediated immunity.

The results with the DHM-rat tumor model more closely resemble the epidemiological findings in which beef protein tends to enhance the incidence of colon tumors, in contrast with non-fat powered milk which tend to inhibit it.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

Robert L. Nutter

Second Advisor

James D. Kettering

Third Advisor

Robert W. Teel

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1986

Date (Title Page)

9-1986

Language

English

Library of Congress/MESH Subject Headings

Colonic Neoplasms; Dietary Fats -- adverse effects; Dietary Proteins -- adverse effects

Type

Thesis

Page Count

vi; 53

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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