title: High-fat diet blocks the inhibition of skin carcinogenesis and reductions in protein kinase C by moderate energy restriction.
abstract: 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.
authors.affiliation: Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68198-6805, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Birt
authors.forename: T
authors.initials: T
authors.lastname: Barnett
authors.forename: P M
authors.initials: PM
authors.lastname: Pour
authors.forename: J
authors.initials: J
authors.lastname: Copenhaver
mesh_terms: D000818:Animals; D001835:Body Weight; D002273:Carcinogens; D002277:Carcinoma / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D003043:Cocarcinogenesis; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D018632:Mice, Inbred SENCAR; D010212:Papilloma / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D011493:Protein Kinase C / Q000378:metabolism*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate
chemical_list: D002273:Carcinogens; D004041:Dietary Fats; D007527:Isoenzymes; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate