Consumption of reduced-energy/low-fat diet or constant-energy/high-fat diet during mezerein treatment inhibited mouse skin tumor promotion.
Previous studies in our laboratory have shown that promotion of two-stage skin carcinogenesis in the SENCAR mouse model was inhibited in mice fed energy-restricted/low-fat diets, and elevated in mice fed high-fat diets. Studies reported here describe the influence of dietary energy restriction from fat and carbohydrate (ER) or high-fat (HF) diet on early promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) and on late promotion by mezerein (MEZ). Female SENCAR mice were initiated topically with 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA) in 0.2 ml acetone at 9 weeks of age. For the following 2 weeks they received 3.2 nmol TPA in 0.2 ml acetone twice weekly, and for the next 16 weeks they received 10 nmol MEZ in 0.2 ml acetone twice weekly. All mice were fed control diet before TPA began and following the final MEZ treatment. Control mice received the control diet (c) throughout TPA and MEZ (C/C). The six experimental groups received: (1) ER diet throughout TPA and MEZ treatment (ER/ER); (2) HF diet throughout TPA and MEZ treatment (HF/HF); (3) ER during TPA (ER/C); (4) ER during MEZ (C/ER); (5) HF diet during TPA (HF/C); or (6) HF diet during MEZ (C/HF). Papilloma incidence and multiplicity, and carcinoma incidence were similarly reduced in the mice fed ER diet during MEZ (ER/ER and C/ER groups). In comparing the HF groups, papilloma multiplicity was highest in the HF/C group, intermediate in the C/C and lowest in the C/HF groups, but papilloma and carcinoma incidences were not modified by the HF diet protocols. Papilloma regression was greater in the C/HF group (27%, 4 regressions/15 tumor-bearing mice) than in the controls (0/18) during weeks 21-23, immediately following the end of MEZ treatment (P < 0.05).
Eppley Institute for Research in Cancer and Allied Diseases, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-6805.
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D018752:Diet, Fat-Restricted; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D004224:Diterpenes; D002149:Energy Intake; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D010212:Papilloma / Q000139:chemically induced* / Q000209:etiology / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000517:prevention & control*; D013729:Terpenes / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate
D002273:Carcinogens; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate