High-fat diet blocks the inhibition of skin carcinogenesis and reductions in protein kinase C by moderate energy restriction

Mol Carcinog. 1996 Jun;16(2):115-20. doi: 10.1002/(SICI)1098-2744(199606)16:2<115::AID-MC8>3.0.CO;2-H.


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 alpha and zeta 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 alpha 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 zeta 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Body Weight
  • Carcinogens
  • Carcinoma / enzymology
  • Carcinoma / etiology
  • Carcinoma / prevention & control
  • Cocarcinogenesis*
  • Dietary Fats / adverse effects*
  • Energy Intake*
  • Female
  • Isoenzymes / metabolism*
  • Mice
  • Mice, Inbred SENCAR
  • Papilloma / enzymology
  • Papilloma / etiology
  • Papilloma / prevention & control
  • Protein Kinase C / metabolism*
  • Skin Neoplasms / enzymology*
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / prevention & control
  • Tetradecanoylphorbol Acetate


  • Carcinogens
  • Dietary Fats
  • Isoenzymes
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate