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

Citation
C. Rodriguez-burford et al., Effects of acute and chronic body weight gain reductions in the evaluationof agents for efficacy in mammary cancer prevention, ONCOL REP, 8(2), 2001, pp. 373-379
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ONCOLOGY REPORTS
ISSN journal
1021-335X → ACNP
Volume
8
Issue
2
Year of publication
2001
Pages
373 - 379
Database
ISI
SICI code
1021-335X(200103/04)8:2<373:EOAACB>2.0.ZU;2-Z
Abstract
Studies were performed to determine the effects of moderate decreases in bo dy weight gain on mammary carcinogenesis. The levels of depressions in weig ht gain were those often observed in the evaluation of chemopreventive agen ts. 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 multiplicitie s, while a 15% chronic reduction significantly decreased cancer numbers (26 %down arrow). A second experiment evaluated the efficacy of toremifene (7.0 mg/kg diet), an estrogen/anti-estrogen, and the effect of toremifene-match ed body weight gain reduction that occurred during the study. Toremifene ca used 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 ex hibited a 67% decrease in the number of mammary cancers, the 'matched body weight reduction' rats which similarly exhibited a 10% decrease in final bo dy weight showed only a 14% decrease in cancer number. Thus, the weight eff ects 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 c hronic body weight gain reduction on mammary cancers induced in older rats (MNU given at 100 days of age). This model more closely resembles the statu s of the breast tissue of mature women currently enrolled in clinical trial s of chemopreventive agents. Under these conditions chronic reductions in b ody weight up to 15% had minimal effects on mammary carcinogenesis. These d ata 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 depression s of body weight gain probably do not play a significant role.