Effects of acute and chronic body weight gain reductions in the evaluation of agents for efficacy in mammary cancer prevention

Rodriguez-Burford,Cristina; Lubet,Ronald A.; Steele,Vernon E.; Eto,Isao; Bandy,Mattie; Juliana,M. Margaret; Weiss,Heidi L.; Grizzle,William E.; Kelloff,Gary J.; Grubbs,Clinton J.

doi:10.3892/or.8.2.373

March-April 2001 Volume 8 Issue 2

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March-April 2001 Volume 8 Issue 2

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Article

Effects of acute and chronic body weight gain reductions in the evaluation of agents for efficacy in mammary cancer prevention

Authors:
- Cristina Rodriguez-Burford
- Ronald A. Lubet
- Vernon E. Steele
- Isao Eto
- Mattie Bandy
- M. Margaret Juliana
- Heidi L. Weiss
- William E. Grizzle
- Gary J. Kelloff
- Clinton J. Grubbs
View Affiliations / Copyright

Affiliations: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Pages: 373-379
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Published online on: March 1, 2001

https://doi.org/10.3892/or.8.2.373
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Abstract

Studies were performed to determine the effects of moderate decreases in body weight gain on mammary carcinogenesis. The levels of depressions in weight gain were those often observed in the evaluation of chemopreventive agents. In the first experiment, the effects of acute and chronic reductions of body weight gain when started after carcinogen treatment were examined in young rats (MNU at 50 days of age). Significant decreases (36%) in mammary cancers occurred in groups of rats that underwent a 12% acute reduction in body weight gain as compared with ad libitum controls. In contrast, chronic weight reductions of up to 12% had minimal effects on cancer multiplicities, while a 15% chronic reduction significantly decreased cancer numbers (26%). A second experiment evaluated the efficacy of toremifene (7.0 mg/kg diet), an estrogen/anti-estrogen, and the effect of toremifene-matched body weight gain reduction that occurred during the study. Toremifene caused a chronic reduction in body weight that resulted in a 10% decrease in final body weight at the end of the study. While toremifene-treated rats exhibited a 67% decrease in the number of mammary cancers, the rats which similarly exhibited a 10% decrease in final body weight showed only a 14% decrease in cancer number. Thus, the weight effects observed with toremifene, similar estrogens/anti-estrogens, and other classes of chemopreventive compounds (where chronic body weight reductions are 10% or less) imply that the body weight reduction has a limited effect on overall chemopreventive activity. A third study examined the effect of chronic body weight gain reduction on mammary cancers induced in older rats (MNU given at 100 days of age). This model more closely resembles the status of the breast tissue of mature women currently enrolled in clinical trials of chemopreventive agents. Under these conditions chronic reductions in body weight up to 15% had minimal effects on mammary carcinogenesis. These data further demonstrated that acute body weight reductions in young rats at the time of carcinogen treatment can be a concern in interpretation of the chemopreventive activity of an agent, but that moderate chronic depressions of body weight gain probably do not play a significant role.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effects of acute and chronic body weight gain reductions in the evaluation of agents for efficacy in mammary cancer prevention

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