The effect of dietary fat on the rapid development of mammary tumors induced by 7,12-dimethylbenz(a)anthracene in SENCAR mice (original) (raw)
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Cancer research, 1992
On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation with 7,12-dimethylbenz(a)anthracene and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol-13-acetate. An inverse correlation (r = -0.92) was observed between papilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidence was also found. The fatty acid composition of epidermal phospholipids reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetate-induced epidermal prostaglandin E2 levels generally decreased with increasing dietary LA. To determine whether this inverse correlation between dietary LA and tumor yield was due to species differences or organ-model differe...
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1995
The effects of pure gamma-linolenic acid (GLA; C18:3, n-6) and dihomo-gamma-linolenic acid (DGLA; C20:3, n-6) were investigated in 7,12-dimethylbenz(~)anthracene (DMBA) (10mg/rat)-induced mammary tumors in Sprague-Dawley rats. 0.15 g of GLA, DGLA, or corn oil (CO) were administered (two times per week) by oral intubation, for 12 weeks to rats maintained on a 5% (w/w) CO diet. Tumor incidence, tumor multiplicity, and percent of tumor-bearing rats were highest in the CO group. Tumor multiplicity was significantly reduced in the GLA group (p = 0.015). Feeding of GLA and DGLA resulted in significant alterations in levels of these fatty acids in phospholipids of mammary tissue, thymus, colon, liver, stomach, and ovary. These results suggest that GLA may have a small, but significant, inhibitory effect on the development of DMBA-induced mammary tumors in rats.
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...
Cancer Research, 1997
Previous research showed that treatment with conjugated linoleic acid (CLA) during the period of active mammary gland morphogenesis was sufficient to confer a lasting protection against subsequent mammary tumorigenesis induced by methylnitrosourea. The present study was de signed to characterize certain morphological and biochemical changes of the mammary gland that might potentially render it less susceptible to cancer InductIon. Female Sprague Dawley rats were fed a 1% CLA diet from weaning until about 50 days ofage. The mammary gland parameters under investigation Included (a) the deposition of neutral lipid, (b) the identification and quantification of CLA and its metabolites, (c) the den sity of the epithelium, and (d) the proliferative activity of various struc tin-al components Our results showed that CLA treatment did not affect total fat deposition In the mammary tissue nor the extent of epitheial invasion into the surrounding fat pad but was able to cause a 20% reduction in the density of the ductal-lobular tree as determined by digitized image analysis of the whole mounts This was accompanied by a suppression of bromodeoxyuridine labeling in the terminal end buds and lobuloalveolar buds. The recovery of desaturation and elongation prod ucts of CLA in the mammary gland confirmed our prior suggestion that the metabolism of CLA might be critical to risk modulation. The signifi cance of the above findings was investigated in a mammary carcinogenesis bioassay with the use of the dlmethylbenz[ajanthracene model. When CLA was started at weaning and continued for 6 months until the end of the experiment, this schedule of supplementation produced essentially the same magnitude of mammary tumor inhibition In the dimethylbenz[ajan thracene model as that produced by 1 month of CLA feeding from weaning. The observation Is consistent with the hypothesis that exposure to CIA during the time of mammary gland maturation may modify the developmental potential of a subset of target cells that are normally susceptible to carcinogen-Induced transformation.
Conjugated linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is naturally occurring in meat and dairy products. We have previously reported (Ip, C., Chin, S. F., Scimeca, J. A., and Pariza, M. W. Cancer Res., 5/: 6118-6124, 1991) that 1% CLA in the diet suppressed mammary carcinogenesis in rats given a high dose (10 mg) of 7,12-dimethylbenz(a)anthracene. In the present study, dietary CLA between 0.05 and 0.5% was found to produce a dose-dependent inhibition in mammary tumor yield when fed chronically to rats treated with a lower dose (5 mg) of 7,12-dimethylbenz-(a)anthracene. Short-term CLA feeding for 5 weeks, from weaning to the time of carcinogen administration at 50 days of age, also offered signifi cant protection against subsequent tumor occurrence. This period corre sponds to maturation of the mammary gland to the adult stage in the rat. The inhibitory response to short-term CLA exposure was observed with the use of 2 different carcinogens: 7,12-dimethylbenz(a)anthracene and methylnitrosourea. The fact that CLA was protective in the methylnitrosourea model suggests that it may have a direct modulating effect on susceptibility of the target organ to neoplastic transformation. The proliferative activity of the mammary epithelium was assessed by the incor poration of bromodeoxyuridine.
Cancer Research, 1994
Conjugated linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is naturally occurring in meat and dairy products. We have previously reported (Ip, C., Chin, S. F., Scimeca, J. A., and Pariza, M. W. Cancer Res., 5/: 6118-6124, 1991) that 1% CLA in the diet suppressed mammary carcinogenesis in rats given a high dose (10 mg) of 7,12-dimethylbenz(a)anthracene. In the present study, dietary CLA between 0.05 and 0.5% was found to produce a dose-dependent inhibition in mammary tumor yield when fed chronically to rats treated with a lower dose (5 mg) of 7,12-dimethylbenz-(a)anthracene. Short-term CLA feeding for 5 weeks, from weaning to the time of carcinogen administration at 50 days of age, also offered signifi cant protection against subsequent tumor occurrence. This period corre sponds to maturation of the mammary gland to the adult stage in the rat. The inhibitory response to short-term CLA exposure was observed with the use of 2 different carcinogens: 7,12-dimethylbenz(a)anthracene and methylnitrosourea. The fact that CLA was protective in the methylnitrosourea model suggests that it may have a direct modulating effect on susceptibility of the target organ to neoplastic transformation. The proliferative activity of the mammary epithelium was assessed by the incor poration of bromodeoxyuridine.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2016
We investigated how different doses of conjugated linoleic acids applied for various periods of time influence breast cancer risk and fatty acids profile in serum of rats treated or not with 7,12-dimethylbenz [a]anthracene (DMBA). We also search for interactions among parameters describing health conditions and cancer risk. Animals were divided into 18 groups with different diet modifications (vegetable oil, 1.0%, 2.0% additions of CLA) and different periods of supplementation. In groups treated with DMBA mammary adenocarcinomas appeared. Due to the complexity of experiment apart from statistical analysis a chemometric tool-Partial Least Square method was applied. Analysis of pairs of correlated parameters allowed to identify some regularities concerning the relationships between fatty acid profiles and clinical features of animals. Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration. These two factors underlined the differences in fatty acids profiles among clusters of animals.
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.
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.
Conjugated Linoleic Acids (Cla) Decrease the Breast Cancer Risk in Dmba-Treated Rats
Acta poloniae pharmaceutica
The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5...