Inhibition of Chemically Induced Mammary and Colon Tumor Promotion by Caloric Restriction in Rats Fed Increased Dietary Fat (original) (raw)
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Cancer Research, 1984
Enhancement of mammary tumor formation by dietary fat may be mediated via increased caloric intake. Three experiments were performed to study this relationship in 7,12-dimethylbenz(a)anthracene (DMBA)-treated female Sprague-Dawley rats: (a) high-or low-fat isocaloric diets were fed in a crossover design; (b) low-fat, high-calorie and high-fat, low-calorie diets were fed in a crossover design; (c) pair-fed rats were restricted to 60% of the calories of controls with ad libitum access to food beginning 10 days after DMBA administration. The pair-fed rats received daily 60% of calories, the same level of fiber, and 115% more fat than did rats fed ad libitum. Tumor yield but not tumor incidence was greater in rats fed high-fat rather than low-fat isocaloric diets prior to initiation of tumorigenesis. A low-fat, highcalorie diet led to more tumor incidence and yield than was associated with feeding of a high-fat, low-calorie diet. Caloric restriction (although with concomitant intake of more fat) led to complete inhibition of tumor formation. These results indicate that both high-fat and high-calorie diets exhibit cocarginogenic, not merely promotional, properties. Caloric intake may be a greater determinant than dietary fat of a tumor-enhancing regi men. Finally, restriction of caloric intake during promotion mark edly suppresses tumor formation, despite the increased fat con tent of the restricted diet, suggesting a permissive role for calories in tumor formation. The possibility remains that altera tions in levels of other dietary components could also have contributed to the observed effects.
Lipids, 1986
The experiments reported are part of our effort to dissociate the tumor-enhancing effects of dietary fat and high caloric intake. Rats either were fed ad libitum diets containing 4% corn oil or their calories were restricted by 40% and their diets contained 13.1% corn oil. Incidence of 7,12-dimethylbenz(a)anthracene {DMBAHnduced mammary tumors was 80% in rats fed ad libitum and 20% in those fed the calorie-restricted diets. Incidence of 1,2-dimethylhydrazine (DMH)oinduced colon tumors was 100% in rats fed ad libitum and 53% in those whose caloric intake was restricted by 40%. The tumor yield {tumors per tumor-bearing rat) was significantly lower in rats on caloric restriction. In another series, rats were fed diets containing 5, 15 or 20% corn oil ad libitum or were fed calorie-restricted (by 25%} diets which provided 20 or 26.6% corn oil (therefore, the same absolute amount of fat was consumed in each of the pair-fed groups). Tumor incidence and tumor yield in the two calorie-restricted groups were similar to those seen in the rats fed 5% fat ad libitum; tumor burden {total g of tumor) was 45-65% lower in the calorie-restricted rats. The data suggest that caloric intake is a more stringent determinant of tumor growth than fat intake. 272-274 (1986).
Effects of caloric restriction and dietary fat on epithelial cell proliferation in rat colon
Cancer research, 1993
Epidemiological studies indicate that caloric intake and dietary fat content influence colonic carcinogenesis. In rodents, caloric restriction reduces, and some fats increase, carcinogen-induced colon cancer incidence. The present study was designed to investigate the effects of caloric restriction on colonic cell proliferation (CCP) in carcinogen-treated or control rats fed low- or high-fat diets. F344 rats were treated with azoxymethane (15 mg/kg x2) and then fed an isocaloric AIN 76A diet containing either 5 or 23% corn oil, ad libitum or calorie-restricted to 70 or 80% of the kilocalories consumed by ad libitum rats. Biopsies of the distal colon were taken at 10 and 20 weeks, and rats were sacrificed at 21 or 34 weeks on the experimental diets. Distal CCP was determined by microautoradiography after [3H]thymidine labeling in vitro or presacrifice administration in vivo. The labeling index and number of labeled cells per crypt column were significantly reduced by caloric restrict...
Inhibition of dmba-induced mammary tumorigenesis by caloric restriction in rats fed high-fat diets
International Journal of Cancer, 1989
Most previous studies on the inhibiting effect of ciiloric restriction during promotion of DMBA-induced mammary carcinogenesis have used low to moderate levels of dietary fat, i.e., about 4 to 14% by weight. The current study was designed to test whether a moderate degree of caloric restriction, 25%, would inhibit tumor growth in rats fed the equivalent of 20% dietary fat which approximates human consumption in affluent countries, Rats were fed diets ad libitum that contained 5, I 5 or 20% corn oil. Groups of cats were pair-fed to the last 2 groups, but subjected to a 2554 caloric restriction. These groups were fed 20 or 26.7% corn ail so that absolute fat intake in the paired groups was identical. Significant inhibition of tumor incidence, tumor weight, tuimor burden, body fat deposition, and fasting serum insulin were observed in the 2 calorically restricted groups. We concllude that moderate caloric restriction is significantly more effective in inhibiting tumor growth than is the promoting effect of diets high in fat. Total body weight, body fat and serurn insulin concentrations may be better correlates of risk of developing mammary tumors than is dietary fat.
Cancer research, 1992
We recently reported (J. Leyton et al., Cancer Res., 51: 907-915, 1991) an inverse correlation between skin tumor number and level of dietary linoleic acid (LA) in SENCAR mice following an initiation-promotion protocol. These results differed from the reported (C. Ip et al., Cancer Res., 45: 1997-2001, 1985) positive correlation between dietary LA and tumor incidence for the rat mammary gland. The goal of the study reported here was to determine whether this dissimilarity was due to organ site or species differences. Female SENCAR mice were fed 1 of 3 15% fat diets containing LA at levels of 0.8, 4.5, and 8.4% before, during, and after intragastric administration of 6 mg (1 mg/week) 7,12-dimethylbenz(a)anthracene. A positive correlation between level of dietary LA and mammary tumor incidence was observed such that for the first 15 weeks, the incidence was greatest in the 8.4% LA diet group, followed by the 4.5% and then the 0.8% LA groups. Distinct dietary effects on latency were al...
Cancer research, 1989
Caloric restriction (CR) inhibits many neoplastic diseases in rodents, yet the biochemical mechanism(s) for these effects are poorly understood. We have examined the effects of ad libitum (AL) feeding with 25 or 40% CR on the promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in virgin female Sprague-Dawley rats. Further, we have also studied the influence of chronic CR on temporal alterations in circulating insulin, insulin-like growth factor I/somatomedin C, insulin-like growth factor II/multiplication-stimulating activity, and epidermal growth factor levels at 0, 1, 3, 5, 11, and 20 weeks in carcinogen- and vehicle-treated animals. Tumor incidence and multiplicity were markedly inhibited (P less than 0.05) with increasing CR. Fasting serum insulin-like growth factor I/somatomedin C levels exhibited a significant acute decline with CR at 1 and 3 weeks, but were comparable to AL-fed controls throughout the remainder of the 5-month study, despite continued dif...
Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis
Carcinogenesis, 1997
CO 80214, USA chemical species (adrenal cortical steroid) that may be 1 To whom correspondence and reprint requests should be addressed involved in mediating the protective effects of energy Caloric restriction has documented beneficial effects on restriction. These data indicate the feasibility of identifying numerous diseases including cancer, yet the mechanism(s) a chemical basis for the protective effect of caloric restricthat accounts for these wide ranging benefits is unknown.
International Journal of Cancer, 1987
The aim of this study was to separate the effects of calorie a&). Since fat iS not carcinogenic per se, it may exert its intake on tumorigenesis from those of fat content and fat influence during cell exposure to a carcinogenic stimulus and composition in an animal model. Our principal observations tumor manifestation (Carroll, 1975; Carroll et al., 1985). were the following. (I) Decreasing the calorie level by 30% Besides the total fat level, the quality of dietary lipids apsignificantly inhibited tumor development in any observed parameter of tumorigenesis, independently of the level of fat. peared to influence the Of lesions. (2) The fat content of semi-synthetic diets, although varying Interestingly, an enhancement (Hopkins et 2 1981; Chan and by 44.4%, did not significantly influence mammary tumori
Cancer research, 1990
We have extracted from the literature data from 100 animal experiments, involving 7838 rats and mice, which compared the effects of different levels of dietary fat and/or calorie intake on the development of mammary tumors. Both higher calorie intake (P less than 0.0001) and higher fat intake (P less than 0.0001) independently increased mammary tumor incidence in Sprague-Dawley rats and in mice, as judged from analyses combining ad libitum feeding experiments and restricted feeding experiments. The effect of fat was two thirds the magnitude of the calorie effect in both Sprague-Dawley rats and mice. In ad libitum feeding experiments, a modest but significant (P less than 0.0001) average increase in body weight was found in animals fed high fat diets. However, these differences in body weight did not correspond to differences in mammary tumor incidence. The effect of log body weight on the log odds of tumor incidence was not significant (P = 0.16), while dietary fat intake significan...
Effects of fat and fiber on human colon cancer xenografted to athymic nude mice
Digestive Diseases and Sciences, 1991
The effects of unsaturated fat and fiber (cellulose) on the growth of human colon cancer explanted to athymic nude mice was evaluated. Eighty-seven male nude mice bearing xenografts of human HT29 or WiDr colon cancer were divided into three groups of equal weight and tumor volume. Each group was fed one of three diets: normal fat~no fiber (N/N), high fat~no fiber (H/N) or high fat~high fiber (H/H). To equalize caloric intake, animals in the H/N group received 4 g of food per day and the other animals were fed 5 g of food per day. At sacrifice tumor volume and weight was recorded, and tumors were analyzed for protein and DATA content and ornithine decarboxylase activity. Tumor volume, weight, and protein were greater in the H/N group compared to the N/N group for both colon cancer cell lines. Tumor DNA content was greater in the HT29 H/N group compared to the N/N group (P < 0.05) and tumor ornithine decarboxylase activity in the WiDr H/N group was greater than the N/N animals (P < 0.002). The tumor growthpromoting effects of the high unsaturated fat diet were attenuated by the addition of fiber. Animal weight was higher in the H/N group compared to the N/N and H/H groups. This study suggested that a high-fat diet stimulated and fiber decreased the growth of human colon cancer explanted to athymic nude mice. The growth-promoting effects of a high-fat diet in colorectal cancer may be due in part to a circulating trophic factor since these tumors were remote from the large intestine.