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-st age skin carcinogenesis in the SENCAR mouse model was inhibited in mic e fed energy-restricted/low-fat diets, and elevated in mice fed high-f at diets. Studies reported here describe the influence of dietary ener gy restriction from fat and carbohydrate (ER) or high-fat (BF) diet on early promotion by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and on late promotion by mezerein (MEZ). Female SENCAR mice were initiated t opically 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 th ey 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 treatmen t. 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 treatme nt (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 i ncidence and multiplicity, and carcinoma incidence were similarly redu ced in the mice fed ER diet during MEZ (ER/ER and C/ER groups), In com paring the HF groups, papilloma multiplicity was highest in the HF/C g roup, intermediate in the C/C and lowest in the C/HF groups, but papil loma and carcinoma incidences were not modified by the HF diet protoco ls. Papilloma regression was greater in the C/HF group (27%, 4 regress ions/l5 tumor-bearing mice) than in the controls (0/18) during weeks 2 1-23, immediately following the end of MEZ treatment (P < 0.05).