Carcinogenesis Advance Access published online on February 4, 2004
Carcinogenesis, doi:10.1093/carcin/bgh105
© 2004 by Oxford University Press
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CARCINOGENESIS
1 Department of Urology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655
* Corresponding author. E-mail: homma-uro{at}umin.ac.jp.
Received 25 August 2003
; revised 20 January 2004
; accepted 26 January 2004
The association between prostate cancer risk and dietary fat consumption is well documented and partly explained by accelerated lipid peroxidation. We explored the possible effects of high dietary cholesterol on carcinogenesis and oxidative stress in the prostate of ACI/Seg rats. The rats develop prostate cancer spontaneously late in the life, providing an appropriate model to explore prolonged dietary conditions. Two groups of 20-week-old male rats, 28 each, were fed either a basal diet or a basal diet supplemented with 1% cholesterol (high cholesterol diet), and killed at 100 weeks of age. Rats on the high cholesterol diet developed adenocarcinoma in the ventral prostate more frequently (26% versus 4%, P=0.023). In the repeat study, 26 rats each were treated similarly and killed at 80 weeks for histology and oxidative stress assay. Oxidative stress was assessed by measuring the plasma and intra-prostatic levels of vitamin E, vitamin C, uric acid and the oxidized and reduced forms of coenzyme Q9. The relative amount of oxidized form of coenzyme Q9 is a sensitive marker of oxidative stress. Rats on the high cholesterol diet demonstrated a higher incidence of atypical prostatic hyperplasia (24% versus 4%, P=0.049). Also the prostate showed a 2-fold increase (203% of the control) in the relative amounts of the oxidized form of coenzyme Q9 and reciprocal reduction of vitamin C (9.5% of the control) and uric acid (46% of the control) levels (P<0.01), with a minimal change in vitamin E. The plasma levels of these compounds were not affected by dietary conditions. These results indicated that long-term feeding of a 1% cholesterol diet promoted carcinogenesis and tissue oxidative stress in rat prostate. The role of dietary fat and oxidative stress in prostate carcinogenesis needs further investigation.
carcinogenesis, cholesterol, prostate, oxidative stress, coenzyme Q
Promotion of carcinogenesis and oxidative stress by dietary cholesterol in rat prostate
2 Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656
3 National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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