The effect of the level of dietary corn oil on mouse skin carcinogenesis

To investigate the effects of two levels of dietary corn oil on tumorigenesis, semipurified diets containing 5% or 10% corn oil were fed during the promotion stage of a mouse skin carcinogenesis model. Sencar mice were initiated with 10 nmol dimethylbenz[a]anthracene (DMBA) and promoted with either 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) or 40 mg benzoyl peroxide twice weekly for 24 or 52 weeks, respectively. No significant differences in kilocalories of food consumed or body weights were observed between the diet groups during the study. Fatty acid profiles of the epidermal phospholipids reflected dietary fat intake. For example, high levels of linoleate and low levels of arachidonate were found in the phosphatidylcholine fraction from mice fed the 10% corn oil diet compared with 5% corn oil. When the diets were fed during TPA promotion, the papilloma incidence after 11 weeks of treatment for the 5% corn oil group was 77% and 37% for the 10% corn oil group. By 15 weeks of TPA treatment, papilloma incidence between the diet groups was similar, and later, carcinoma incidence and yield were not different between the two groups. For the animals treated with benzoyl peroxide, there was only a slight but not significant difference in papilloma and carcinoma appearance. In parallel studies, ornithine decarboxylase activity, vascular permeability, hyperplasia, and prostaglandin E2 (PGE2) levels were elevated in the epidermis after promoter treatment, but only hyperplasia and PGE2 synthesis tended to reflect the dietary effects on tumor appearance. These data suggest that the quantity of dietary corn oil at the two levels tested, 5% and 10%, altered epidermal phospholipid fatty acid composition and PGE2 levels and had modest effects on the modulation of tumorigenesis in this skin model.     

The effect of various dietary fats on skin tumor initiation

The type of dietary fat has been shown to modulate the initiation stage of mammary tumorigenesis, with saturated fat fed before and/or during carcinogen treatment resulting in increased tumor incidence. This study was designed to determine whether different types of dietary fat alter the initiation stage of skin carcinogenesis by use of the initiation‐promotion mouse skin carcinogenesis model. Sencar mice were divided into three groups and maintained on one of the experimental diets. The AIN‐76‐based diets consisted of 10% total fat with various types of fat: 8.5% menhaden oil plus 1.5% corn oil, 8.5% coconut oil plus 1.5% corn oil, and 10% corn oil. After three weeks mice were initiated with 10 nmol dimethyl‐benz[a]anthracene (DMBA). Two weeks later, all mice were switched to a diet containing 5% corn oil. Promotion began four weeks after initiation with twice‐weekly application of 1 μg 12‐O‐tetradecanoylphorbol‐13‐acetate and continued for 12 weeks. No statistically significant differences in kilocalories of food consumed or body weights were observed between diet groups during the study. The final papilloma incidence, yield, and size were not significantly different among the diet groups. In a parallel study, [³H]DMBA binding to epidermal DNA showed no dietary differences. Unlike the mammary carcinogenesis model, these data suggest that the type of fat fed during DMBA initiation had minimal effects on this stage of skin carcinogenesis.     

The effect of various dietary fats on skin tumor initiation.

The type of dietary fat has been shown to modulate the initiation stage of mammary tumorigenesis, with saturated fat fed before and/or during carcinogen treatment resulting in increased tumor incidence. This study was designed to determine whether different types of dietary fat alter the initiation stage of skin carcinogenesis by use of the initiation-promotion mouse skin carcinogenesis model. Sencar mice were divided into three groups and maintained on one of the experimental diets. The AIN-76-based diets consisted of 10% total fat with various types of fat: 8.5% menhaden oil plus 1.5% corn oil, 8.5% coconut oil plus 1.5% corn oil, and 10% corn oil. After three weeks mice were initiated with 10 nmol dimethylbenz[a]anthracene (DMBA). Two weeks later, all mice were switched to a diet containing 5% corn oil. Promotion began four weeks after initiation with twice-weekly application of 1 microgram 12-O-tetradecanoylphorbol-13-acetate and continued for 12 weeks. No statistically significant differences in kilocalories of food consumed or body weights were observed between diet groups during the study. The final papilloma incidence, yield, and size were not significantly different among the diet groups. In a parallel study, [3H]DMBA binding to epidermal DNA showed no dietary differences. Unlike the mammary carcinogenesis model, these data suggest that the type of fat fed during DMBA initiation had minimal effects on this stage of skin carcinogenesis.     

Inhibition of DMBA-induced mouse skin tumorigenesis by garlic oil and inhibition of two tumor-promotion stages by garlic and onion oils

A single 2-mg dose of garlic oil applied 30 minutes before a single carcinogenic dose of 7,12-dimethylbenz[a]-anthracene (DMBA) inhibited papilloma production in Sencar mice. The three groups were controls (Group 1), garlic oil applied 30 minutes before DMBA (Group 2), and garlic oil applied 30 minutes after DMBA (Group 3). The percents of mice with papillomas at 20 weeks were 94, 72, and 79, respectively. The decreases in Groups 2 and 3 were significant. The number of papillomas per mouse was 4.2 +/- 0.5 (Group 1), 2.3 +/- 0.8 (Group 2), and 3.4 +/- 0.6 (Group 3). The decrease in Group 2 was significant. A single 5-mg dose of garlic oil maximally inhibited DMBA-induced epidermal DNA synthesis by 86% when applied two hours before the carcinogen. Two-stage promotion in DMBA-initiated Sencar mice was achieved by twice-weekly applications of 8.5 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 2 weeks followed by twice-weekly applications of 8.5 nmol of mezerein for 18 weeks. The oils were applied 30 minutes after each promotion by TPA or mezerein. Single doses of 1 mg onion or garlic oil inhibited the first and second stages of promotion. The groups used were control (Group 1), garlic oil applied after stage 1 (Group 2), onion oil applied after stage 1 (Group 3), propenyl sulfide applied after stage 1 (Group 4), garlic oil applied after stage 2 (Group 5), onion oil applied after stage 2 (Group 6), and propenyl sulfide applied after stage 2 (Group 7). The percent of mice with papillomas was significantly decreased by all agents in Groups 2-7. The data are 81, 83, 91, 68, 96, and 86, respectively. The number of papillomas per mouse was significantly reduced by onion and garlic oils but not by propenyl sulfide. The data are 9.4 +/- 0.8, 6.3 +/- 0.7, 7.4 +/- 0.5, 9.2 +/- 1.2, 3.7 +/- 0.9, 6.2 +/- 0.6, and 9.1 +/- 1.4 for Groups 1-7, respectively. Onion and garlic oils inhibited the TPA-stimulated DNA synthesis when given as single doses of 5 mg one hour before TPA. The inhibition by garlic oil was most effective when given one hour before TPA but was evident when given from two hours before to two hours after TPA. These results, and those of others (AS Sadhana, Cancer Lett, 40, 193-197, 1988), who obtained inhibition of initiation, indicate that onion and garlic oils inhibit all stages of mouse skin tumorigenesis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of dietary fat intake on local recurrence and progression of metastases arising from MDA-MB-435 human breast cancer cells in nude mice after excision of the primary tumor.

This study was performed to evaluate the effect of dietary fat on the recurrence and metastasis of human breast cancer solid tumors growing in nude mice after surgical excision of the primary tumor. Female nude mice were fed either a high- (23% corn oil) or a low-fat (5% corn oil) diet, and 7 days later 1 x 10(6) MDA-MB-435 human breast cancer cells were injected into a thoracic mammary fat pad. Tumors at the injection site grew more rapidly in the animals fed the high-fat diet. Nineteen of 30 animals in each dietary group had tumors with a surface are > or = 1 cm2 within 10 weeks of injection, at which point the tumors were excised and the animals were followed for another eight weeks. Tumors recurred at the excision site in 8 of 19 animals fed the high-fat diet and in 9 of 19 animals fed the low-fat diet; however, the growth rate was more rapid in the group fed the high-fat diet. Lung metastases occurred with similar frequency in the two groups with local recurrences, but with a positive correlation between recurrent tumor weight (greater in the animals fed the high-fat diet) and the severity of lung metastatic involvement. In the mice without recurrence, 4 of 11 (36%) animals in the group fed the high-fat diet had macroscopic lung metastases compared with only one mouse, with minimal involvement, in the group fed the low-fat diet.     

Effects of type and amount of dietary fat on mouse skin tumor promotion

In a previous study (Cancer Res 51, 907, 1991) in which we found an inverse relationship between quantity of dietary corn oil and saturated fat, in a constant 15% fat diet, on the tumor promotion stage of skin carcinogenesis, it was not clear whether one or both types of fat played a modulatory role. The purpose of the present study therefore was to compare the effect of 1) increasing corn oil in corn oil-only diets and 2) increasing saturated fat, with a constant level of 5% corn oil, on tumor promotion. In the first study, the effects of five levels of dietary corn oil (5%, 10%, 15%, 20%, and 25%) on the incidence and rat of papilloma and carcinoma development were determined in female Sencar mice fed these diets one week after initiation with 7,12-dimethylbenz[a]anthracene and three weeks before the start of promotion with 12-O-tetradecanoylphorbol-13-acetate. A papilloma incidence of 100% was reached first in the 5% corn oil group, at 10 weeks, followed by the 10% group at 13 weeks and the 15% and 20% group at 16 weeks. The highest corn oil group achieved a 90% incidence. There were marked differences in latency of carcinoma development among the diet groups. At Week 29, the cumulative carcinoma incidence was 56% and 32%, respectively, in the 5% and 10% corn oil groups, whereas the incidence in the two highest corn oil (20% and 25%) groups was only 8% and 4%, respectively. In the second study, the effects of diets containing 5% corn oil and increasing levels of coconut oil (5%, 10%, 15%, and 20%) on the incidence and rat of papilloma and carcinoma development were determined, as described above. No significant difference in latency or incidence of papillomas or carcinomas was noted among these saturated fat diet groups. It thus appears that higher levels of dietary corn oil are associated with a reduced cancer incidence in this model system.     

Inhibition of DMBA‐induced mouse skin tumorigenesis by garlic oil and inhibition of two tumor‐promotion stages by garlic and onion oils

A single 2‐mg dose of garlic oil applied 30 minutes Before a single carcinogenic dose of 7, 12‐dimethylbenz[a]‐anthracene (DMBA) inhibited papilloma production in Sencar mice. The three groups were controls (Group 1), garlic oil applied 30 minutes before DMBA (Group 2), and garlic oil applied 30 minutes after DMBA (Group 3). The percents of mice with papillomas at 20 weeks were 94, 72, and 79, respectively. The decreases in Groups 2 and 3 were significant. The number of papillomas per mouse was 4.2 ± 0.5 (Group 1), 2.3 ± 0.8 (Group 2), and 3.4 ± 0.6 (Group 3). The decrease in Group 2 was significant. A single 5‐mg dose of garlic oil maximally inhibited DMBA‐induced epidermal DNA synthesis by 86% when applied two hours before the carcinogen. Two‐stage promotion in DMBA‐initiated Sencar mice was achieved by twice‐weekly applications of 8.5 nmol of 12‐O‐tetradecanoytphorbol‐13‐acetate (TPA) for 2 weeks followed by twice‐weekly applications of 8.5 nmol of mezereinfor 18 weeks. The oils were applied 30 minutes after each promotion by TPA or mezerein. Single doses of 1 mg onion or garlic oil inhibited the first and second stages of promotion.

The groups used were control (Group 1), garlic oil applied after stage 1 (Group 2), onion oil applied after stage 1 (Group 3), propenyl sulfide applied after stage 1 (Group 4), garlic oil applied after stage 2 (Group 5), onion oil applied after stage 2 (Group 6), and propenyl sulfide applied after stage 2 (Group 7). The percent of mice with papillomas was significantly decreased by all agents in Groups 2–7. The data are 81, 83, 91, 68, 96, and 86, respectively. The number of papillomas per mouse was significantly reduced by onion and garlic oils but not by propenyl sulfide. The data are 9.4 ± 0.8, 6.3 ± 0.7, 7.4 ± 0.5, 9.2 ± 1.2, 3.7 ± 0.9, 6.2 ± 0.6, and 9.1 ± 1.4 for Groups 1–7, respectively. Onion and garlic oils inhibited the TPA‐stimulated DNA synthesis when given as single doses of 5 mg one hour before TPA. The inhibition by garlic oil was most effective when given one hour before TPA but was evident when given from two hours before to two hours after TPA. These results, and those of others (AS Sadhana, Cancer Lett, 40, 193–197, 1988), who obtained inhibition of initiation, indicate that onion and garlic oils inhibit all stages of mouse skin tumorigenesis. Inhibition of DNA synthesis may be part of the mechanisms involved.     

The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB/c mice

This study investigated the effect of diet, exercise and , 7,12-dimethylbenz(a)anthracene (DMBA), a mammary-tumor carcinogen, on food intake, energy consumption, body weight and body composition in virgin female BALB/c mice. Interactions were examined among three diet conditions (standard AIN-76A, restricted AIN-76A and high fat AIN-76A diet), two exercise conditions (with and without treadmill exercise) and two treatment conditions (carcinogen or corn oil sham). Mice were randomized to one of 12 groups at 6 wk of age; beginning at 8 wk of age, all mice received either 7,12-dimethylbenz(a)anthracene (1 mg/0.2 mL corn oil) or 0.2 mL of corn oil via gastric tube once each week for six consecutive weeks. Exercise in a rotating-drum treadmill was initiated at 10 wk of age and was increased to a final rate of 6 m/min for 60 min, 5 d/wk. Mice were killed at 24 wk of age, confirmed to be tumor-free and analyzed for protein and fat content, from which body energy was calculated. Energy consumption was highest in the standard diet-fed groups followed by the high fat diet-fed groups and the restricted diet-fed groups. The groups fed the standard diet and restricted diet had similar body weight and carcass energy. Exercise or DMBA treatment generally reduced food consumption, energy intake, body weight and carcass energy. In summary, diet, exercise and DMBA all had pronounced effects on energy consumption, which in turn affected body composition. These treatments may influence expression of breast cancer via their effects on body composition.     

Caraway oil inhibits skin tumors in female BALB/c mice

Caraway oil, supplemented in diet or painted on the skin, inhibited 7,12‐dimethylbenz[a]anthracene‐ (DMBA) and croton oil‐induced skin tumors in female BALB/c mice. The inhibition was manifested by disappearance of carcinomas, reduced incidence and number of papillomas, delay of their appearance, retardation of their development, and regression of already established papillomas. Caraway oil is more effective when topically applied than when supplemented in the diet.     

Effects of a long-chain fatty amine on mammary carcinogenesis induced in female Sprague-Dawley rats by DMBA.

Reports that protein kinase C is inhibited by sphingosine and other long-chain amines and the suggestion that promotion of mammary carcinogenesis by dietary fat is mediated by protein kinase C prompted us to investigate the effects of a long-chain amine, 1-octadecylamine, on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats fed a high-fat diet. Rats fed the amine sulfate at a level of 0.01% in a semipurified diet containing 20% corn oil developed more tumors than those fed the high-fat diet alone, although body weight gain was inhibited slightly. Rats fed the amine sulfate at 0.1% of the diet developed very few tumors compared with those fed either the high-fat diet or a low-fat diet containing 5% corn oil. At the higher level, the C18 amine also caused a marked inhibition of body weight gain.     

Comparison of ultraviolet light‐induced skin carcinogenesis and ornithine decarboxylase activity in Sencar and Hairless SKH‐1 mice fed a constant level of dietary lipid varying in corn and coconut oil

To investigate the effect of various levels of corn oil and coconut oil on ultraviolet (UV) light‐induced skin tumorigenesis and ornithine decarboxylase (ODC) activity, Sencar and SKH‐1 mice were fed one of three 15% (weight) fat semipurified diets containing three ratios of com oil to coconut oil: 1.0%:14.0%, 7.9%:7.1%, and 15.0%:0.0% in Diets A, B, and C, respectively. Groups of 30 Sencar and SKH‐1 mice were fed one of the diets for three weeks before UV irradiation; then both strains were UV irradiated with an initial dose of 90 mJ/cm². The dose was given three times a week and increased 25% each week. For Sencar mice (irradiated 33 wks for a total dose of 48 J/cm²), tumor incidence reached a maximum of 60%, 60%, and 53% for Diets A, B, and C, respectively, with an overall average of one to two tumors per tumor‐bearing animal. For the SKH‐1 mice (irradiated 29 wks for a total dose of 18 J/cm²), all diet groups reached 100% incidence by 29 weeks, with approximately 12 tumors per tumor‐bearing mouse. No significant effect of dietary corn oil/coconut oil was found for tumor latency, incidence, or yield in either strain. The effect of increasing com oil on epidermal ODC activity in chronically UV‐irradiated Sencar and SKH‐1 mice was assessed Three groups of mice from each strain were fed one of the experimental diets and UV irradiated for six weeks. Sencar mice showed no increase in ODC activity until six weeks of treatment, when the levels of ODC activity in the UV‐irradiated mice fed Diet A were significantly higher than those in mice fed Diet B or Diet C: 1.27, 0.55, and 0.52 nmol/mg protein/hr, respectively. In the SKH‐1 mice, ODC activity was increased by the first week of UV treatment, and by three weeks of treatment a dietary effect was observed: ODC activity was significantly higher in mice fed Diet C (0.70 nmol/mg protein/hr) than in mice fed Diet A (0.18 nmol/mg protein/hr). Although there was no significant effect of dietary corn oil/coconut oil on UV‐induced tumor incidence, the data indicate that chronically UV‐irradiated hairless SKH‐1 mice are more susceptible to UV‐induced skin carcinogenesis than Sencar mice and that this susceptibility is correlated with increases in ODC activity, a parameter of cell proliferation.     

The effect of treadmill exercise on azoxymethane-induced intestinal neoplasia in the male Fischer rat on two different high-fat diets

A total of 120 eight-week-old male rats were exposed to azoxymethane (15 mg/kg body wt in saline s.c.) on Days 1, 4, and 8. Two days after the last injection of carcinogen, the rats were randomized into four experimental groups: two groups were given a chow high in corn oil (23% corn oil) and two groups a chow high in coconut oil (21% coconut oil and 2% corn oil). One group on each chow was kept sedentary, and one group was exposed to moderate exercise, running 2 km/day on weekdays for 38 weeks. At the end of the experiment, the exercising and sedentary rats fed coconut oil were significantly heavier than those fed corn oil. Among the rats fed the high-fat corn oil diet, exercise reduced the number of animals developing carcinomas in the colon (sedentary, 10; exercise, 0) and in the small intestine (sedentary, 5; exercise, 0). The same tendency was observed in the rats fed the coconut oil diet: colon (sedentary, 6; exercise, 3) and small intestine (sedentary, 3; exercise, 2). In the sedentary rats fed the high corn oil diet, 16 intestinal carcinomas were recorded; none were found in the exercised group. In the rats fed the high coconut oil diet, nine carcinomas were recorded in the sedentary groups as opposed to five in the exercised rats. Rats fed the high-fat coconut oil developed significantly fewer neoplasms than the rats fed the equally high-fat corn oil diet.     

Effects of dietary lipid saturation on prolactin secretion, carcinogen metabolism and mammary carcinogenesis in rats

Isoenergetic diets containing 20% corn oil, 20% beef tallow, or an equal mixture of 10% corn oil and 10% beef tallow (mixed fat) were fed to 30 rats per diet for 28 weeks following weaning. DMBA [7,12-dimethylbenz(a)anthracene] was administered (1.75 mg/100 g body weight) in a single oral dose after 4 weeks of feeding. After 28 weeks, 70% of the rats fed corn oil had mammary tumors versus 47% for mixed fat and 30% for tallow. Diet had no effect on the number of tumors per tumor-bearing rat or the proportion of tumors that were adenocarcinomas. Other rats assigned to each of the three diets were killed at the time corresponding to DMBA administration for examination of hepatic mixed-function oxidase activity. NADPH cytochrome c reductase activity and cytochrome P-450 content were higher in rats fed corn oil or mixed fat rather than tallow. However, no significant differences in aryl hydrocarbon hydroxylase, glutathione transferase, and uridine-diphosphoglucuronide transferase activities were observed. The effects of dietary fat saturation on enzyme activity failed to show a clear association with DMBA carcinogenesis. In other rats assigned to the three dietary treatments for 4 or 16 weeks, lipid saturation did not change serum prolactin (PRL) concentrations during diestrus or proestrus. PRL secretion was examined following a provocative stimulus (perphenazine) in rats fed the experimental diets for 4 or 10-22 weeks. Although perphenazine increased serum PRL and depleted the pituitary of PRL, differences in dietary lipid saturation caused no significant changes in these indices. These data show that the incidence of mammary tumors in rats fed high fat diets (20% by weight) was greater in those fed corn oil compared to beef tallow. The effect of dietary lipid source on tumorigenesis was not associated with changes in carcinogen-metabolizing enzyme activity or PRL secretion.     

Changes in selenium and antioxidant status during DMBA-induced mammary carcinogenesis in rats

Female weanling Sprague-Dawley rats were used to examine the changes that occurred in selenium and antioxidant status during the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Animals were fed an AIN-76 diet, modified to contain 20% fat (3:1 wt/wt, lard:corn oil) and 0.1, 0.035, 0.1, 1.0, 2.0 or 4.0 mg Se/kg diet. At wk 5, rats in groups 2-6 were administered by intragastric tube 4.32 mg of DMBA dissolved in corn oil. Control rats received corn oil only. A blood sample was removed from the tail vein and analyzed for selenium-dependent glutathione peroxidase (Se-GSHPx) and superoxide dismutase (SOD) activity at wk 5, and every 4 wk until wk 25. At the end of the experiment, rats were classified by tumor status, and each diet group was subdivided into two groups: those rats remaining free of tumors for 25 wk and those with tumors. DMBA treatment caused an initial decrease in erythrocyte SeGSHPx and SOD activity compared to untreated control rats. SeGSHPx activity in rats with tumors remained lower than controls, while SeGSHPX activity increased in rats with no tumors. These changes, however, were not associated with any changes in lipid peroxidation.     

The effect of dietary fat on metastasis of the Lewis lung carcinoma and the BALB/c mammary carcinoma

The effect of feeding mice diets high in beef tallow (high in saturated fat) or corn oil (high in polyunsaturated fat) on the production of lung metastases by the Lewis lung carcinoma and the BALB/c mammary tumor was determined. Diets were fed ad libitum, and the mice fed the high-fat (24.6%) diets consumed more calories and gained more weight than those fed the control (5%) diets. With the Lewis lung carcinoma, we found that both high-fat diets significantly increased the growth of the primary tumor in the footpad as well as the number of spontaneous metastases produced after the primary was removed; this was in comparison with results from the appropriate control diets. With the BALB/c mammary tumor, the high-fat beef tallow diet (but not the corn oil diet) significantly increased the number of lung metastases formed after tail vein injection. In addition, the group given the control corn oil diet had more metastases than the group given the control beef tallow diet. Overall, these studies showed that the consumption of high-fat/high-calorie diets increased metastasis compared to the consumption of high-fat/high-calorie diets increased metastasis compared to the consumption of low-fat diets. However, the results varied depending on the tumor model used and the type of fat.     

Reversal of the promotional effect of high-fat diet on mammary tumorigenesis by subsequent lowering of dietary fat

Female Sprague-Dawley rats were given 7,12-dimethylbenz(a)anthracene at 50 days of age to induce mammary tumors, and beginning one week later were fed a high-fat, semipurified diet containing 20% sunflowerseed oil to promote tumor development. After another 7 weeks, when one third of the rats had palpable mammary tumors, the rats were randomly assigned to five groups of 31 animals each, with the same number of tumor-bearers in each group. One group was continued on the high-fat diet, another was given a fat-free diet, and the three remaining groups were fed diets containing 10% lard, butter, or coconut oil, respectively. During the next 29 weeks, rats fed the diets containing 0% or 10% fat developed significantly fewer tumors than those continued on the 20% fat diet. The diets containing 10% fat suppressed tumorigenesis at least as effectively as the fat-free diet. Rats fed the 10% butter and 10% lard diets had growth rates comparable to those fed the 20% sunflowerseed-oil diet throughout, and evidence of essential fatty acid deficiency was seen only in rats on the fat-free diet. These results provide additional evidence that high-fat diets promote development of mammary cancer and suggest that reducing the level of dietary fat might help to prevent the development and recurrence of breast cancer in humans.     

Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice

Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5-week-old, female CD(1) mice were used. Both groups had skin cancer initiated with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA application. Tumor incidence, the number of mice containing at least one tumor, was 100% and 93%, and multiplicity, the average number of tumors per mouse, was 20.8 and 16.3 per mouse after 20 weeks of promotion in the control and pomegranate seed oil-treated groups, respectively (P <.05). In a second experiment, two groups each consisting of three CD(1) mice were used to assess the effect of pomegranate seed oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an important event in skin cancer promotion. Each group received a single topical application of TPA, with the experimental group receiving a topical treatment 1 h prior with 5% pomegranate seed oil. The mice were killed 5 h later, and ODC activity was assessed by radiometric method. The experimental group showed a 17% reduction in ODC activity. Pomegranate seed oil (5%) significantly decreased (P <.05) tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlight the potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.     

The interaction of dietary fat and antiestrogen treatment on DMBA‐induced mammary tumors in the rat

This study was designed to determine whether an estrogenic mechanism is in volved in dietary fat‐modulated tumor development and growth. Female Sprague‐Dawley rats were placed on a semipurified low‐fat (2% fat), high‐saturated fat (20% fat), or high‐polyunsaturatedfat (20% fat) diet at 21 days of age. A single dose of7,12‐dimethylbenz[at]anthracene (DMBA, 10 mg) was administered intragastrically at 50 days of age. Two studies were performed. One tested the effectiveness of antiestrogen treatment (either tamoxifen or analog II) on tumor development when it was given one week prior to and one week after DMBA treatment in animals consuming a high‐polyunsaturated fat diet. The second six‐week study tested the antiestrogen effectiveness in arresting tumor growth and in producing regressions of established DMBA‐induced tumors in rats consuming various levels and types of fat.

The results of these studies indicate that both antiestrogens employed reduced the rate of growth and increased the number of regressions of established DMBA‐induced tumors. In general, this was true in animals fed diets with a high content of either saturated or polyunsaturated fats and to a lesser extent in animals fed a low‐fat diet. Tamoxifen produced a somewhat greater reduction in the growth of established tumor than did analog II. However, analog II, which is a more biologically “pure” antiestrogen, reduced the incidence of animals with mammary tumors and total tumor burden when administered one week beforeandone week after DMBA dosing. Tamoxifen, which is a partial estrogen‐agonist, did not alter tumor incidence, but it did reduce the total tumor burden under these same experimental conditions. We concluded that estrogens may be partially responsible for the observed dietary fat enhancement of breast tumor development.     

Papilloma and carcinoma production in DMBA-initiated, onion oil-promoted mouse skin

Groups of 20 females Ha/ICR mice were initiated with 25 micrograms 7,12-dimethylbenz[a]anthracene (DMBA) and promoted one week later with topical treatments three times per week of 5 micrograms phorbol myristate acetate (PMA) and/or onion oil or garlic oil. Promotion was continued for 49 weeks in most experiments. Promotion was continued for 60 weeks in the experiment that evaluated the effect of time intervals between PMA and garlic oil. All experiments were conducted with 0.2 ml acetone solutions of agents. Onion oil, but not garlic oil, was a weak promoter in mouse skin. A 1-mg dose produced five papillomas in three mice and one carcinoma in 330 days (18 survivors). The 10-mg dose was more effective; it produced cumulative yields of 56 papillomas in 14 mice and 7 carcinomas in 4 mice in 345 days (14 survivors). Onion oil is neither an initiator nor a whole carcinogen. The effects of intervals between PMA and a 1-mg dose of onion or garlic oil were determined. These intervals were -2 hrs, -1 hr, -0.5 hr, +0.5 hr, +1 hr, and +2 hrs with respect to time of PMA application. Maximal inhibition of papillomas by onion oil was observed at the +0.5-hr interval and was similar to that previously reported. Garlic oil is not a promoter. It inhibited papillomas at the +0.5-hr, +1.0-hr, and +2.0-hr intervals but did not appear to affect carcinoma production.     

The interaction of dietary fat and antiestrogen treatment on DMBA-induced mammary tumors in the rat

This study was designed to determine whether an estrogenic mechanism is involved in dietary fat-modulated tumor development and growth. Female Sprague-Dawley rats were placed on a semipurified low-fat (2% fat), high-saturated fat (20% fat), or high-polyunsaturated fat (20% fat) diet at 21 days of age. A single dose of 7,12-dimethylbenz[a]anthracene (DMBA, 10 mg) was administered intragastrically at 50 days of age. Two studies were performed. One tested the effectiveness of antiestrogen treatment (either tamoxifen or analog II) on tumor development when it was given one week prior to and one week after DMBA treatment in animals consuming a high-polyunsaturated fat diet. The second six-week study tested the antiestrogen effectiveness in arresting tumor growth and in producing regressions of established DMBA-induced tumors in rats consuming various levels and types of fat. The results of these studies indicate that both antiestrogens employed reduced the rate of growth and increased the number of regressions of established DMBA-induced tumors. In general, this was true in animals fed diets with a high content of either saturated or polyunsaturated fats and to a lesser extent in animals fed a low-fat diet. Tamoxifen produced a somewhat greater reduction in the growth of established tumor than did analog II. However, analog II, which is a more biologically "pure" antiestrogen, reduced the incidence of animals with mammary tumors and total tumor burden when administered one week before and one week after DMBA dosing. Tamoxifen, which is a partial estrogen-agonist, did not alter tumor incidence, but it did reduce the total tumor burden under these same experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)