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High‐fat diet blocks the inhibition of skin carcinogenesis and reductions in protein kinase C by moderate energy restriction
Author(s) -
Birt Diane F.,
Barnett Tracy,
Pour Parviz M.,
Copenhaver James
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199606)16:2<115::aid-mc8>3.0.co;2-h
Subject(s) - dmba , protein kinase c , calorie , medicine , 12 o tetradecanoylphorbol 13 acetate , endocrinology , biology , calorie restriction , tetradecanoylphorbol acetate , carcinogenesis , kinase , biochemistry , cancer , phorbol ester
The aim of this investigation was to determine the impact of dietary energy restriction (ER) with control (C) and high‐fat (HF) diets on two‐stage skin carcinogenesis and on the expression of specific isoforms of protein kinase C (PKC). Skin carcinogenesis was initiated on SENCAR mice with 10 nmol of 7,12‐dimethylbenz[a]anthracene (DMBA) in 0.2 mL of acetone and then promoted with twice weekly treatments of 3.2 nmol of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in 0.2 mL of acetone for 18 wk. The experimental diets fed during TPA treatment and for 10 wk after the last TPA treatment were formulated with C (10% calories from fat) and HF (42% calories from fat) levels for freely fed groups. These diets were restricted by 20% (20% ER/C and 20% ER/HF) and by 40% (40% ER/C and 40% ER/HF). Papilloma incidence was reduced in the mice fed the 20% ER/C, 40% ER/C, and 40% ER/HF diets in comparison with the C, HF, and 20% ER/HF groups. Carcinoma incidence was also reduced in these groups. PKC α and ζ were assessed by western blot analysis in the epidermises of mice pre‐fed the six diets for 8–10 wk (without DMBA or TPA treatment). PKC α was reduced in the particulate fraction by 32–44% in the 20% ER/C, 40% ER/C, and 40% ER/HF groups ( P < 0.005). PKC ζ was reduced by 24–31% in the cytosol of mice fed the 20% ER/C diet and in the particulate fraction of mice fed the 40% ER/C diet ( P < 0.05). The HF diet was able to block the inhibition of skin carcinogenesis and the reduction in the expression of PKC in the epidermis by 20% ER but not by 40% ER. © 1996 Wiley‐Liss, Inc.