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D F Birt

Publications and source records attributed to D F Birt.

At least 55 records · Page 3Linked to original sources
PubMed1992

Influences of sphingosine on two-stage skin tumorigenesis in Sencar mice.

Sphingosine (SPH) was studied as an inhibitor of skin tumor promotion in skin cancer initiated by 7,12-dimethylbenz[a]-anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two tumorigenesis studies were conducted using female Sencar mice treated with 10 nmol DMBA in 0.2 ml acetone at 8 weeks of age and promoted beginning 1 week later with 3.2 nmol TPA applied twice per week. In the high-dose study, 10 mumol SPH was applied 30 min before each TPA treatment. The low-dose study used 0.5, 0.05, or 0.01 mumol treatments with SPH 30 min before TPA. In the high-dose study SPH treatment alone following initiation by DMBA, and SPH treatment preceding TPA in DMBA-initiated mice accelerated the development of papillomas in comparison with the DMBA/TPA-treated group. The low-dose experiment showed no consistent alteration of tumorigenesis by SPH in the DMBA/TPA-treated groups, and low doses of SPH following DMBA did not promote skin tumorigenesis. SPH treatment did not alter body weight in either experiment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Protein kinase C is activated and diacylglycerol is elevated in epidermal cells from Sencar mice fed high fat diets.

Studies reported here determined the effect of dietary fat level on membrane phospholipid composition, phosphoinositide labeling, 1,2-sn-diacylglycerol and protein kinase C activity in epidermal cells from female Sencar mice. Animals were fed either high fat (24.6 g/100 g diet) or control (5 g/100 g diet) diets at constant energy intake for 6 to 7 wk or 15 to 22 wk, and epidermal cells were isolated. The level of phosphatidylinositol was significantly lower in the animals fed the control diet than in the animals fed the high fat diet (0.6 vs. 1.2 nmol/10(6) cells). The fatty acid composition of the phospholipids showed significantly lower arachidonic acid level in phosphatidylinositol when the animals were fed the high fat diet. Protein kinase C activity in the solubilized particulate and soluble fraction of the cells was 131 +/- 18% and 62 +/- 14% greater, respectively, in animals fed the high fat diet compared with animals fed control diet. The level of 1,2-sn-diacylglycerol was significantly higher in animals fed the high fat diet (mean nmol/mg lipid +/- SEM: control, 4.5 +/- 0.5; high fat, 7.0 +/- 0.5). Incorporation of [3H]inositol into inositol lipid was not altered by diet. Because protein kinase C and 1,2-sn-diacylglycerol have been implicated in tumor promotion, the increase in protein kinase C activity and the elevation of 1,2-sn-diacylglycerol in cells from animals fed the high fat diet may be important in the high cancer rate observed with these diets.

Animals↗
PubMed1991

Influence of diet and calorie restriction on the initiation and promotion of skin carcinogenesis in the SENCAR mouse model.

Diets were restricted to 60% of the intake of the control mice by feeding less diet (total diet restriction, TDR) or by feeding fewer calories from fat and carbohydrate (calorie restriction, CR) during the initiation or promotion phases of skin tumorigenesis in female SENCAR mice. Skin cancer was initiated by topical treatment with 10 nmol of 7,12-dimethylbenzanthracene in acetone and promoted by twice weekly treatments with 12-O-tetradecanoylphorbol-13-acetate in acetone for 20 wk. Dietary restriction preceding and during 7,12-dimethylbenzanthracene treatment did not influence skin papilloma or carcinoma yield. Papilloma incidence and the number of papillomas per effective mouse were reduced in mice restricted by both TDR and CR protocols during and following promotion with 12-O-tetradecanoylphorbol-13-acetate. Papilloma size was reduced at experimental wk 16 and 20 in both TDR and CR groups fed these diet regimens during promotion. However, by wk 28 and 32, papilloma sizes were similar in the control and TDR groups, and smaller papillomas were observed only in the CR group. The average carcinoma latency was extended by 26% in the groups restricted during promotion, and incidence was reduced in both groups. The reduction, however, was statistically significant only in the CR group. Body weight gain was reduced during the times when dietary restriction was enforced, and in a short-term study, both restricted diet treatments reduced the percentage of carcass protein.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.

This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose-dependent manner from 1 to 20 mumol. Two tumorigenesis studies were conducted. In the first study, 20 mumol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 mumol of apigenin were used. The papilloma incidence for 0, 5, and 20 mumol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor-bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Comparison of the effects of dietary beef tallow and corn oil on pancreatic carcinogenesis in the hamster model.

We previously reported an enhancement of pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters fed diets containing high levels of corn oil. The research presented here compared diets high in corn oil with those high in beef tallow in the enhancement of pancreatic carcinogenesis. Pancreatic cancer was induced with 20 mg BOP/kg body wt, s.c. administered at 8 weeks of age. One week later, hamsters were assigned to one of five diet treatments: (i) 4.3% corn oil (control); (ii) 20.5% corn oil (high corn oil); (iii) 0.5% corn oil + 3.8% beef tallow (low beef tallow); (iv) 0.6% corn oil + 19.9% beef tallow (high beef tallow); and (v) 5.1% corn oil + 15.4% beef tallow (high fat mixture). These diets were fed until the study ended 84 weeks after BOP treatment. Hamsters were trained through pair feeding to consume the same calorie allotment as the control corn oil group. By the end of the experiment, BOP-treated hamsters that were fed diets containing beef tallow were consistently heavier than those fed corn oil. Survival was longer in hamsters fed the high-beef tallow and high-fat mixture compared with the other diet groups. Tumor data were age adjusted to correct for survival differences. Pancreatic adenoma incidence and multiplicity (no./effective animal) were higher in hamsters fed beef tallow than those fed corn oil diets. Carcinoma in situ multiplicity was elevated in hamsters fed high-fat diets irrespective of the nature of fat fed. Pancreatic adenocarcinoma multiplicity was elevated in hamsters fed the low- or high-beef tallow diets compared with the low- or high-corn oil diets. The mixture of fat resulted in an intermediate yield.

Adenocarcinoma↗
PubMed1990

Reduction in mammary tumorigenesis in the rat by cabbage and cabbage residue.

Mammary cancer was induced in female Sprague-Dawley rats by a single injection of N-methyl-N-nitrosourea (MNU) and rats were randomized to control fat (5%) and high fat (24.6%) diets. In addition, dried cabbage (5 and 10%) and collards (5%) were included in the diets of some animals. No statistically significant differences were observed in food consumption, body wt gain and caloric intake between the MNU-treated and control groups in the rats fed the low-fat diet. However, the groups fed the high-fat diet consumed more than the rats maintained on the control diet. The rats on the control fat diet containing cabbage exhibited a significantly lower incidence of mammary cancer than rats that were fed the control-fat diet without cabbage. This effect was not observed in comparable rats on the high-fat diet. The inhibitory effect on mammary tumorigenesis was demonstrated using a residue obtained from cabbage by exhaustive extraction with methanol, methylene chloride and petroleum ether. These studies reinforce the efficacy of cabbage as a 'suppressor' of cancer in experimental model systems under control-fat dietary conditions.

Animals↗
PubMed1990

The influence of dietary fat on carcinogenesis: lessons from experimental models.

Recent studies of the effects of dietary fat on experimental carcinogenesis have probed the influence of the dietary fat source, the time during carcinogenesis when a high-fat diet is fed, the interactions between fat and calories, and the potential mechanisms for the observed effects of fat on cancer. The essential fatty acids in the fat, the degree of their unsaturation, and the location of the unsaturation are all important in determining the influence of a dietary fat source on carcinogenesis. In addition, alterations in dietary fat can modify various sites and forms of cancer differently. Dietary fat has been clearly shown to be important in the promotion of cancer, and recent studies indicate that dietary fat can also be a factor in the initiation of cancer. Although the calories contributed by a high-fat diet also factor into cancer enhancement, dietary fat appears to contribute more than its high-caloric density. One potential mechanism for the influence of dietary fat on carcinogenesis is through modulating the activation of protein kinase C.

Animals↗
PubMed1989

Enhancement of pancreatic carcinogenesis in hamsters fed a high-fat diet ad libitum and at a controlled calorie intake.

An enhancement of pancreatic cancer induced by N-nitrosobis-(2-oxopropyl)amine (BOP) was reported previously in Syrian hamsters fed high-fat diet following carcinogen treatment. The purpose of our research was to determine if this enhancement was due to the consumption of more calories by the hamsters fed the high-fat diet. Male hamsters were treated with a single injection of BOP (20 mg/kg body weight s.c.) at 8 weeks of age. One week later they started either on a low-fat diet (4.3% corn oil) or a high-fat diet (20.5% corn oil) that was fed until the end of the experiment at 92 weeks after BOP. Diets were fed either ad libitum or in a control-fed protocol. The control-fed groups had equivalent calorie intakes and were restricted slightly in comparison with the ad libitum-fed hamsters. BOP treatment reduced survival slightly but survival did not differ significantly in accordance with dietary assignment. Body weight was elevated in the hamsters fed high-fat diet ad libitum in comparison with those fed low-fat diet ad libitum. However, differences were not observed in hamsters fed low- and high-fat diets by the control-fed protocol. Pancreatic carcinogenesis was enhanced about 3- to 4-fold when hamsters were fed high-fat diet by either protocol. The degree of enhancement did not differ with the feeding regimen. However, the higher death rate with pancreatic cancer occurred earlier in the ad libitum-fed hamsters than in the control-fed hamsters.

Adenocarcinoma↗
PubMed1989

Dietary fat effects on the initiation and promotion of two-stage skin tumorigenesis in the SENCAR mouse.

We investigated the influence of dietary corn oil on initiation of skin tumors in SENCAR mice with 7,12-dimethylbenz(a)anthracene (DMBA) (10 nmol at 8 to 9 wk of age) and the promotion of these tumors with 12-O-tetradecanoylphorbol-13-acetate (TPA) (3.2 nmol twice weekly for 20 wk). Diet high in corn oil (24.6%) was fed, in comparison with control diet (5%), to mice during two time schedules: (a) high-fat diet was fed preceding and for 1 wk following DMBA to assess the effects of high corn oil diet on initiation; and (b) high-fat diet was fed starting at the time of the first TPA treatment (1 wk following DMBA initiation) until the end of the experiment to assess effects of high corn oil diet on promotion. Mice were trained to consume equivalent caloric allotments of the low- and high-fat diets to ensure that the observed effects on tumor development were for dietary fat at constant calorie intake. Feeding high corn oil diet during DMBA treatment did not influence the incidence of skin papilloma or carcinoma, but the number of papillomas per effective mouse was reduced in mice fed the high-fat diet during initiation. Consumption of the high corn oil diet during and following TPA treatment resulted in an increase in the incidence of papillomas up until Wk 14 of the experiment, an increase in the number of papillomas per effective mouse throughout the experiment, and an increase in the number of carcinomas per effective mouse during Wk 25 to 34. However, cumulative carcinoma yield (Wk 25-44) did not differ between the diet groups. Dietary treatment did not influence food consumption, body weight, or survival in the mice treated with DMBA and TPA. Northern blot hybridization studies were carried out on RNA purified from tumors of high- and low-fat mice to determine if diet influenced the pattern of Ha-ras oncogene expression. The results of this experiment indicated that elevated levels of Ha-ras-specific RNA, in comparison with normal epidermal RNA, were present in papillomas and carcinomas from DMBA-initiated, TPA-promoted mice irrespective of the diet the mice were fed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

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.

Animals↗
PubMed1989

The effect of diets enriched in cabbage and collards on murine pulmonary metastasis.

Feeding mice with diets enriched in dried cruciferous vegetables (cabbage and collards) resulted in a significant decrease in the number of pulmonary metastases after the animals were injected intravenously with mammary tumor cells. No differences in weight gain or calorie consumption were seen between the mice fed the different diets. These results support other evidence that diets high in cruciferous vegetables may be beneficial in cancer prevention.

Animals↗
PubMed1989

Acceleration of papilloma growth in mice fed high-fat diets during promotion of two-stage skin carcinogenesis.

The effect of feeding a high-fat diet during the promotion phase of skin tumorigenesis was assessed in SENCAR mice. Tumors were initiated on the backs of mice by application of 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA); the tumors were then promoted beginning one week later with twice weekly treatments of 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) each in 0.2 ml acetone. Control diet containing 5% corn oil was fed from four weeks before until one week after DMBA treatment in all groups. A high-fat diet (24.6% corn oil) was fed from one week after DMBA treatment; the other groups continued on the control diet. Mice were fed ad libitum, and those given the high-fat diet consumed more calories early in the study than the controls did. Treatment with TPA increased calorie consumption throughout the study. Body weights were elevated in mice fed high-fat diets and reduced by TPA treatment. The average number of papillomas per mouse did not differ between the low- and high-fat groups, but papillomas grew more rapidly on the mice fed a high-fat diet than those fed a low-fat diet. The feeding of a high-fat diet following DMBA treatment, in the absence of TPA administration, did not result in promotion of skin tumors. Therefore, a high-fat diet acted as a copromoter of skin tumors in SENCAR mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Inhibition of the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate in mouse skin by sphingosine sulfate.

We investigated the effect of sphingosine sulfate on the induction of ODC (ornithine decarboxylase) activity by TPA (12-O-tetradecanoylphorbol-13-acetate) in mouse skin. When applied topically to the shaved skin of SENCAR mice at dosages of 10-40 mumol per animal, 30 min before the superficial application of 8.5 nmol of TPA, sphingosine sulfate dramatically inhibited the induction of ODC activity by the tumor promoter. Significant inhibition of TPA-induced ODC activity was observed at 4, 6 and 8 h after TPA treatment in separate studies. The results indicate that sphingosine sulfate is an effective inhibitor of ODC induction by TPA in mouse skin.

Animals↗
PubMed1989

Effects of the intake of selected vitamins and minerals on cancer prevention.

This paper provides an overview of our knowledge on the involvement in cancer of vitamins A, C and E and of calcium, selenium and zinc. This work is a background for studies on dietary magnesium's effects on cancer. Consumption of vitamin A and its dietary precursors has been associated with reduced cancer at several sites in human and animal studies. Carcinogenesis studies using several models of cancer have been conducted on the influence of vitamin A deficiency, vitamin A excess and supplementation of vitamin A analogues. Vitamins C and E are effective in the prevention of N-nitroso compound (nitrosamine) formation. Vitamin C is effective in aqueous and vitamin E is effective in non-aqueous media. Both of these vitamins also have inhibited carcinogenesis by preformed carcinogens at several sites, but enhancement has been observed at some sites when excess vitamin treatment was studied. The potential role of calcium in the prevention of colon cancer is being pursed. Few experimental studies have been conducted but data support an effect of calcium on colonic epithelial proliferation. Epidemiological and especially experimental results suggest an inhibition of cancer by dietary selenium. In animal studies, selenium supplementation has been particularly effective in inhibiting colon and mammary carcinogenesis, but enhanced carcinogenesis was observed in some studies on skin, liver and pancreas cancer. Data suggest that zinc deficiency may be a factor in esophageal cancer; however, studies on tumor growth have demonstrated retarded tumor growth in zinc-deficient animals.

Animals↗
PubMed1988

Enhancement of BOP-induced pancreatic carcinogenesis in selenium-fed Syrian golden hamsters under specific dietary conditions.

We measured the effects of dietary selenium (Se) on pancreatic cancer induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP). The animals were fed six experimental diets that contained different combinations of the following: 0.1, 2.5, or 5.0 ppm Se from sodium selenite or 2.5 ppm Se from D,L-selenomethionine in either a low (6.0%)- or high (24.4%)-fat diet. Se treatment was begun four weeks before BOP treatment, and the high-fat diet was fed from one week after the last BOP treatment. No evidence for inhibition of pancreatic cancer by Se was observed; in fact, with some experimental conditions, high-Se diets increased the pancreatic carcinoma yield. However, the dietary conditions needed for enhancement differed between the sexes. The male hamsters that received the high-fat diet containing 2.5 ppm Se had more carcinomas than did males given the 0.1 ppm Se level. Carcinoma yields in females did not differ between these diets. Females that received 2.5 ppm Se from D,L-selenomethionine had a greater pancreatic carcinoma yield that did those given 0.1 ppm Se diet. However, carcinoma yields did not differ in males fed these diets. Acinar cell nodule yields were generally reduced in hamsters given the high-Se diets, especially when Se levels in the high-fat diets were compared. Prefeeding 0.1 or 2.5 ppm Se did not influence the elution constants of pancreatic DNA from ductal cells, indicating no effect of Se on the repair of BOP-induced, single-strand breaks in DNA from these cells. Measurements in acinar cells suggested a more rapid repair of single-strand breaks in hamsters prefed 2.5 ppm Se than in those prefed 0.1 ppm Se.

Animals↗
PubMed1987

Effect of L-tryptophan excess and vitamin B6 deficiency on rat urinary bladder cancer promotion.

To further evaluate the role of tryptophan and vitamin B6 in bladder carcinogenesis, male Fischer 344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) in semipurified diet or were given semipurified diet alone for 4 weeks. One week later, rats from each group were assigned for the remainder of the experiment to one of four experimental diets, labeled as follows: group 1, control semipurified; group 2, L-tryptophan excess (2%); group 3, vitamin B6-deficient (1.0 mg/kg diet); or group 4, L-tryptophan excess, plus vitamin B6-deficient diet. All surviving rats were killed at 80 weeks of the experiment. Throughout the study, body weights were reduced in the groups fed FANFT and, at 70 and 80 weeks, body weights were reduced in the groups given tryptophan excess. The incidence of urinary bladder carcinoma was highest in the group treated with FANFT, followed by diet with control tryptophan and vitamin B6 levels (40%). The disease incidence was reduced in the vitamin B6-deficient group (13%) and of an intermediate range in the groups fed a tryptophan excess with or without vitamin B6 deficiency (28-29%). Tumors at other sites were greatest in number in FANFT-treated rats fed vitamin B6-deficient diet with excess tryptophan and were significantly fewer in FANFT-treated rats fed vitamin B6-deficient diet alone. Animals given diet deficient in vitamin B6 consistently had depressed levels of alanine aminotransferase activity and plasma pyridoxyl phosphate. FANFT pretreatment decreased alanine aminotransferase activities in rats in some groups and the feeding of tryptophan had variable effects on alanine aminotransferase and plasma pyridoxyl phosphate levels. Urinary tryptophan metabolites were influenced by all treatments, but the results did not correlate with tumor yields. Urinary bladder ornithine decarboxylase activity was not altered in vitamin B6-deficient female rats. These results do not support the hypothesis that increased dietary L-tryptophan promotes bladder carcinogenesis in rats, but other dietary factors might modify the process following FANFT initiation.

Alanine Transaminase↗
PubMed1987

Dietary fat regulation of the association of protein kinase C activity with epidermal cell membranes.

An apparent redistribution of protein kinase C activity was noted in the particulate and soluble fractions of basal epidermal cells isolated from mice receiving semi-purified diets varying in fat content. An increase in the amount of protein kinase C activity in the particulate fraction and a decrease in the soluble fraction were observed with the mice fed high-fat (24.6% corn oil) diet as compared with those given the low-fat (5% corn oil) diet. Increased levels of phospholipids and an increase in 18:2 and 18:3 side chains of the phospholipids were observed with the high-fat diet.

Animals↗