The combined effects of dietary protein and fat on 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats (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.
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, 1980
Following 7,12-dimethylbenz[a]anthracene (DMBA) administration, increased tumor incidence and tumor yield were observed in intact rats fed a 20% corn oil diet compared to those fed a 0.5% corn oil diet. Elevated serum prolactin levels (determined at proestrus) were also found in the former group of animals. In order to delineate whether this was responsible for the promoting effect of dietary fat in DMBA-induced mammary carcinogenesis, rats fed these two diets were subjected to electrolytic lesion of the median eminence that resulted in higher circulating prolactin concentrations. Sham-operated animals were used as controls. Results showed that this endocrine manipulation increased the tumor incidence in the low-fat group nearly 3-fold, but it failed to elicit further enhancement in the high-fat rats. Although the serum prolactin level in the low-fat-lesioned rats was comparable to that in the high-fat-lesioned rats, the tumor incidence in the former group still lagged behind that i...
Breast Cancer Research and Treatment, 2004
Effects of a high corn oil and a high olive oil diet on the histopathologic characteristics of rat dimethylbenz(α)anthracene-induced mammary adenocarcinomas were investigated in comparison with those of a control low-fat diet. Two experimental series (A and B) studied the influence of a high corn oil diet on the initiation and the promotion of mammary carcinogenesis, while another one (C) assessed the effects of the two dietary lipids on the promotion. Nine parameters have been analyzed and a new histologic grading method, adapted to rat tumors, has been applied in each carcinoma. High corn oil diets, particularly when acting as promoters, associated with higher-grade carcinomas than control (p p
Cancer Research, 1982
The interaction of dietary fat and the thymus in the induction of mammary tumors by dimethylbenz(a)anthracene has been examined in female Sprague-Dawley rats. In these experi ments, rats fed diets of 0.5% (low fat), 5% (normal fat), or 20% (high fat) corn oil from weaning (21 days of age) were thymectomized or sham thymectomized at 35 days of age and were given 5 mg of dimethylbenz(a)anthracene at 55 days of age. Thymectomy exerted a protective effect in rats fed low and normal fat diets, and this was not reversed by Thymosin Frac tion V. In high fat-fed rats, tumorigenesis was increased com pared to the low fat groups, and in addition, the protective effect of thymectomy was absent. This differential effect of thymectomy could not be explained on the basis of changes in prolactin concentration, since prolactin levels were decreased in all dietary groups. Neither diet nor thymectomy affected corticosterone levels or the estrus cycle of mature rats. Periph eral blood lymphocytes were, however, decreased by both thymectomy and increasing the fat content of the diet. It is hypothesized that the promoting effect of dietary fat on dimethylbenz(a)anthracene-induced mammary tumorigenesis is me diated via the immune system, although a role for the endocrine system still cannot be ruled out.
International Journal of Immunopathology and Pharmacology, 2009
The effects of diet, of non-steroidal anti-inflammatory drugs, or of their combination on carcinogenesis continue to be a case for controversy. Diets that are high in fat have been linked to increased risk of various tumors. At the same time there is substantial, but not conclusive, evidence that the risk of breast and colon cancer correlates with total fat intake rather than a specific type of fat. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs) have been studied extensively because they appear to delay or inhibit the development of malignant and pre-malignant lesions. 7,12-Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce carcinogenesis in a number of rat animal models. The present study attempts to identify the effects on DMBA-induced tumor growth (a) of diets rich in fat and (b) of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.
Mammary Carcinogenesis in Rats Fed Different Amounts and Types of Fat
Cancer Research, 1981
Rats fed 20% corn oil or lard showed increased 7,12-di methylbenzanthracene-induced mammary tumorigenesis and slightly increased growth rate compared to rats fed 5% fat; 20% corn oil accelerated sexual maturation, but 20% lard did not. In contrast, diets high in beef fat (30%) depressedtumor Induction by 7,1 2-dimethylbenzanthracene or N-fluorenyla cetamide compared to a diet containing 15% vegetableoil; dietary lipotrope content had no effect on tumorigenesis. Fur ther studies are neededof the effects of type and amountof dietary fat on mammary tumorigenesis in several model sys tems.
Serum cholesterol and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis
Cancer Letters, 1981
Diet-induced changes in serum cholesterol levels and their relationship to mammary carcinogenesis initiated by 7,12dimethylbenz[a] anthracene (DMBA) were studied in female Sprague-Dawley rats. DMBA was given to rats subjected to 3 dietary treatments: (1) a semipurified, cholesterolfree diet (SP); (2) the same diet with 1.5% cholesterol and 0.5% bile salts added (CB); (3) diet CB, until administration of DMBA and then switched to diet SP. Tumor yield per rat was increased in rats fed diet CB, but incidence and tumor size were similar among all 3 groups. Rats maintained on diet SP alone had a higher percentage of histologically benign tumors. Hypercholesterolemia of dietary origin appears to enhance slightly chemical carcinogenesis in this model.
Lipids, 1988
The comparative effects of high-fat diets {20%, w/w} on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz{a}anthracene {DMBA}-induced rats were studied using diets containing 20% primrose oil {PO}, 20% menhaden oil {MO) or 20% corn oil {CO). Sprague-Dawley rats fed the PO or MO diet had 21% or 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically {i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid {GLA}. Arachidonic acid {AA} levels were significantly higher {p < 0.05) in PO-fed than in CO-or M(~fed rats. MO-fed rats had significantly higher levels of plasma palm/tic acid, while palmitoleic, eicosapentaenoie {EPA) and docosahexaenoic (DHA} acids were detected only in MO-fed rats. As expected, linoleic acid {LA} and AA levels were lower {p < 0.05) in the MOfed rats than in POor CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2-10 times higher than in mammary fat pads of control rats. The synthesis of PGEI and LTB4 was significantly {p < 0.05} higher in PO-fed rats than in CO-fed or MO-fed rats, although PGE values were significantly {p < 0.05} higher in CO-fed rats than in MO or PO groups. The synthesis of eicosanoids in both mammary fat pads and mammary carcinomas of MO-fed rats was lower {p < 0.05} than in tissues of rats fed either CO or PO diets due to less AA precursor being fed and/or to competition between n-6 and n-3 fatty acids for cyclooxygenase and lipoxygenase. The ratios of monc~ enoic to dienoic eicosanoids in both mammary fat pads and mammary carcinomas were higher in the PO group than in the MO or CO groups. These results suggest that inclusion of GLA {PO feeding} or EPA and DHA {MO feeding} in the diet may decrease malignancy by altering eicosanoid profiles.
Effects of dietary primrose oil on mammary tumorigenesis induced by 7,12-dimethylbenz(a) anthracene
Lipids, 1987
The mammary tumor-promoting effect of a high-fat diet containing 20% evening primrose oil (PO) was compared to that of a 20% corn oil (CO) diet. Mammary tumors were induced in female Sprague-Dawley rats using 10 mg (Study 1) and 5 mg (Study 2} 7,12-dimethylbenz(a)anthracene (DMBA). The 10 mg dose of DMBA gave a total mammary tumor incidence of 47% in rats fed the PO diet and 80% for those fed the CO diet. When only adenocarcinomas were counted, the malignant mammary tumor incidences were 41% in rats fed the PO diet and 73% in rats fed the CO diet. In a second study using 5 mg DMBA to induce mammary tumors, total tumor incidences were 50% for PO-fed rats and 63% for those receiving a CO diet. Again, when only adenocarcinomas were counted, tumor incidences were 27% for PO-and 63% for COdieted rats. Analysis of plasma fatty acid profiles indicated that animals fed a 20% PO diet showed significant increases in 18:3 and 20:4 fatty acids and significant decreases in 16:0 and 18:1 compared to animals fed a 20% CO diet. These results indicate that the mammary tumor promoting effect of a diet containing 20% fat can be diminished by substituting PO for CO. Moreover, the promoting effect on mammary cancer by a high-fat diet could be depressed by feeding a source of y-linolenic acid (GLA).