Recent evidence suggests that enhancement of carcinogenesis in animals fed high fat diet may be related to elevated calorie intake or improved calorie utilization in these animals. Since a mechanism for the increase in cancer rate by a high fat diet has not been identified for any site at which dietary fat enhances cancer, it is possible that effects of high fat diet in providing calories or influencing calorie utilization may be important in the observed effects on carcinogenesis. However, early investigations on dietary fat and calorie effects on skin carcinogenesis indicated that high fat intake enhanced tumor development at various levels of calorie intake. Since the two-stage model of skin carcinogenesis is an excellent means for assessing effects on initiation (by dimethylbenzanthracene, DMBA) and promotion (by 12-0-tetradecanoylphorbol-13-acetate, TPA) of epithelial cancers and because dietary fat and calorie effects on the model have not been reported, the following studies are proposed: 1) determination of the effect of dietary fat on two-stage carcinogenesis. Low and high fat diets will be fed to SENCAR mice during DMBA initiation only, or during promotion with or without TPA. 2) Assessment of an effect of dietary restriction on two stage-skin carcinogenesis by 2 methods: a) restriction of a complete diet to 60% of ad libitum consumption, or b) allowing access to a diet providing 60% of the calories but equivalent amounts of vitamins, minerals and fiber as consumed by the ad libitum group. 3) Comparison of the effect on two-stage skin carcinogenesis of removal of fat calories with removal of carbohydrate calories. 4) Measurement of the effects of each of the dietary fat and restriction protocols on oncogene expression during mouse skin tumorigenesis. Preliminary work indicated that Ha-ras expression elevation was an early event in two-stage skin carcinogenesis and dietary effects on this event have not been reported. 5) Study the influence of the dietary fat and restriction protocols on membrane lipids and protein kinase C (PKC) activity. Recent reaults demonstrated increased PKC activity in the particulate fraction of basal epidermal cells from mice fed a high fat-high calorie diet and decreased levels of PKC activity in the soluble fraction of cells from these animals, in comparison with mice fed low fat diets.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA042986-01
Application #
3184815
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
Overall Medical
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Birt, D F; Yaktine, A; Duysen, E (1999) Glucocorticoid mediation of dietary energy restriction inhibition of mouse skin carcinogenesis. J Nutr 129:571S-574S
Birt, D F (1995) Dietary modulation of epidermal protein kinase C: mediation by diacylglycerol. J Nutr 125:1673S-1676S
Kris, E S; Choe, M; Luthra, R et al. (1994) Protein kinase C activity is reduced in epidermal cells from energy-restricted SENCAR mice. J Nutr 124:485-92
Birt, D F; Pelling, J C; Anderson, J et al. (1994) Consumption of reduced-energy/low-fat diet or constant-energy/high-fat diet during mezerein treatment inhibited mouse skin tumor promotion. Carcinogenesis 15:2341-5
Birt, D F; Copenhaver, J; Pelling, J C et al. (1994) Dietary energy restriction and fat modulation of protein kinase C isoenzymes and phorbol ester binding in Sencar mouse epidermis. Carcinogenesis 15:2727-32
Birt, D F; Kris, E S; Choe, M et al. (1992) Dietary energy and fat effects on tumor promotion. Cancer Res 52:2035s-2039s
Choe, M; Kris, E S; Luthra, R et al. (1992) Protein kinase C is activated and diacylglycerol is elevated in epidermal cells from Sencar mice fed high fat diets. J Nutr 122:2322-9
Birt, D F; Pelling, J C; White, L T et al. (1991) Influence of diet and calorie restriction on the initiation and promotion of skin carcinogenesis in the SENCAR mouse model. Cancer Res 51:1851-4
Birt, D F; White, L T; Choi, B et al. (1989) Dietary fat effects on the initiation and promotion of two-stage skin tumorigenesis in the SENCAR mouse. Cancer Res 49:4170-4
Birt, D F; Pelling, J C; Tibbels, M G et al. (1989) Acceleration of papilloma growth in mice fed high-fat diets during promotion of two-stage skin carcinogenesis. Nutr Cancer 12:161-8

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