Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets

Thomas W M Boileau, Zhiming Liao, Sunny H Kim, Stanley Lemeshow, John W. Erdman, Steven K. Clinton

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Abstract

Background: Consumption of tomato products or lycopene and energy restriction have been hypothesized to reduce the risk of human prostate cancer. We investigated the effects of these dietary variables in a rat model of prostate carcinogenesis. Methods: Male rats (n = 194) treated with N-methyl-N-nitrosourea and testosterone to induce prostate cancer were fed diets containing whole tomato powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or control beadlets. Rats in each group were randomly assigned to either ad libitum feeding or 20% diet restriction. Differences between Kaplan-Meier survival curves for diet composition or restriction were tested with the log-rank test. Cox proportional hazards models were developed to examine the combined effect of diet composition and restriction on survival. Statistical tests were two-sided. Results: Risk of death with prostate cancer was lower for rats fed the tomato powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.59 to 0.93; P = .009). In contrast, prostate cancer-specific mortality of the control and lycopene-fed rats was similar (P = .63). The proportions of rats dying with prostate cancer in the control, lycopene, and tomato powder groups were 80% (95% CI = 68% to 89%), 72% (95% CI = 60% to 83%), and 62% (95% CI = 48% to 75%), respectively. Rats in the diet-restricted group experienced longer prostate cancer-free survival than rats in the ad libitum-fed group (HR = 0.68, 95% CI = 0.49 to 0.96; P = .029). The proportion of rats that developed prostate cancer was 79% (95% CI = 69% to 86%) for ad libitum-fed rats and 65% (95% CI = 54% to 74%) for rats fed restricted diets. No interactions were observed between diet composition and dietary restriction. Conclusions: Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis, suggesting that tomato products contain compounds in addition to lycopene that modify prostate carcinogenesis. Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms.

Original languageEnglish (US)
Pages (from-to)1578-1586
Number of pages9
JournalJournal of the National Cancer Institute
Volume95
Issue number21
StatePublished - Nov 5 2003
Externally publishedYes

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Methylnitrosourea
Lycopersicon esculentum
Powders
Testosterone
Prostate
Carcinogenesis
Diet
Prostatic Neoplasms
Confidence Intervals
lycopene
Safety Management
Survival
Kaplan-Meier Estimate
Phytochemicals
Proportional Hazards Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. / Boileau, Thomas W M; Liao, Zhiming; Kim, Sunny H; Lemeshow, Stanley; Erdman, John W.; Clinton, Steven K.

In: Journal of the National Cancer Institute, Vol. 95, No. 21, 05.11.2003, p. 1578-1586.

Research output: Contribution to journalArticle

Boileau, Thomas W M ; Liao, Zhiming ; Kim, Sunny H ; Lemeshow, Stanley ; Erdman, John W. ; Clinton, Steven K. / Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 21. pp. 1578-1586.
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abstract = "Background: Consumption of tomato products or lycopene and energy restriction have been hypothesized to reduce the risk of human prostate cancer. We investigated the effects of these dietary variables in a rat model of prostate carcinogenesis. Methods: Male rats (n = 194) treated with N-methyl-N-nitrosourea and testosterone to induce prostate cancer were fed diets containing whole tomato powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or control beadlets. Rats in each group were randomly assigned to either ad libitum feeding or 20{\%} diet restriction. Differences between Kaplan-Meier survival curves for diet composition or restriction were tested with the log-rank test. Cox proportional hazards models were developed to examine the combined effect of diet composition and restriction on survival. Statistical tests were two-sided. Results: Risk of death with prostate cancer was lower for rats fed the tomato powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95{\%} confidence interval [CI] = 0.59 to 0.93; P = .009). In contrast, prostate cancer-specific mortality of the control and lycopene-fed rats was similar (P = .63). The proportions of rats dying with prostate cancer in the control, lycopene, and tomato powder groups were 80{\%} (95{\%} CI = 68{\%} to 89{\%}), 72{\%} (95{\%} CI = 60{\%} to 83{\%}), and 62{\%} (95{\%} CI = 48{\%} to 75{\%}), respectively. Rats in the diet-restricted group experienced longer prostate cancer-free survival than rats in the ad libitum-fed group (HR = 0.68, 95{\%} CI = 0.49 to 0.96; P = .029). The proportion of rats that developed prostate cancer was 79{\%} (95{\%} CI = 69{\%} to 86{\%}) for ad libitum-fed rats and 65{\%} (95{\%} CI = 54{\%} to 74{\%}) for rats fed restricted diets. No interactions were observed between diet composition and dietary restriction. Conclusions: Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis, suggesting that tomato products contain compounds in addition to lycopene that modify prostate carcinogenesis. Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms.",
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AU - Liao, Zhiming

AU - Kim, Sunny H

AU - Lemeshow, Stanley

AU - Erdman, John W.

AU - Clinton, Steven K.

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N2 - Background: Consumption of tomato products or lycopene and energy restriction have been hypothesized to reduce the risk of human prostate cancer. We investigated the effects of these dietary variables in a rat model of prostate carcinogenesis. Methods: Male rats (n = 194) treated with N-methyl-N-nitrosourea and testosterone to induce prostate cancer were fed diets containing whole tomato powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or control beadlets. Rats in each group were randomly assigned to either ad libitum feeding or 20% diet restriction. Differences between Kaplan-Meier survival curves for diet composition or restriction were tested with the log-rank test. Cox proportional hazards models were developed to examine the combined effect of diet composition and restriction on survival. Statistical tests were two-sided. Results: Risk of death with prostate cancer was lower for rats fed the tomato powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.59 to 0.93; P = .009). In contrast, prostate cancer-specific mortality of the control and lycopene-fed rats was similar (P = .63). The proportions of rats dying with prostate cancer in the control, lycopene, and tomato powder groups were 80% (95% CI = 68% to 89%), 72% (95% CI = 60% to 83%), and 62% (95% CI = 48% to 75%), respectively. Rats in the diet-restricted group experienced longer prostate cancer-free survival than rats in the ad libitum-fed group (HR = 0.68, 95% CI = 0.49 to 0.96; P = .029). The proportion of rats that developed prostate cancer was 79% (95% CI = 69% to 86%) for ad libitum-fed rats and 65% (95% CI = 54% to 74%) for rats fed restricted diets. No interactions were observed between diet composition and dietary restriction. Conclusions: Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis, suggesting that tomato products contain compounds in addition to lycopene that modify prostate carcinogenesis. Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms.

AB - Background: Consumption of tomato products or lycopene and energy restriction have been hypothesized to reduce the risk of human prostate cancer. We investigated the effects of these dietary variables in a rat model of prostate carcinogenesis. Methods: Male rats (n = 194) treated with N-methyl-N-nitrosourea and testosterone to induce prostate cancer were fed diets containing whole tomato powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or control beadlets. Rats in each group were randomly assigned to either ad libitum feeding or 20% diet restriction. Differences between Kaplan-Meier survival curves for diet composition or restriction were tested with the log-rank test. Cox proportional hazards models were developed to examine the combined effect of diet composition and restriction on survival. Statistical tests were two-sided. Results: Risk of death with prostate cancer was lower for rats fed the tomato powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.59 to 0.93; P = .009). In contrast, prostate cancer-specific mortality of the control and lycopene-fed rats was similar (P = .63). The proportions of rats dying with prostate cancer in the control, lycopene, and tomato powder groups were 80% (95% CI = 68% to 89%), 72% (95% CI = 60% to 83%), and 62% (95% CI = 48% to 75%), respectively. Rats in the diet-restricted group experienced longer prostate cancer-free survival than rats in the ad libitum-fed group (HR = 0.68, 95% CI = 0.49 to 0.96; P = .029). The proportion of rats that developed prostate cancer was 79% (95% CI = 69% to 86%) for ad libitum-fed rats and 65% (95% CI = 54% to 74%) for rats fed restricted diets. No interactions were observed between diet composition and dietary restriction. Conclusions: Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis, suggesting that tomato products contain compounds in addition to lycopene that modify prostate carcinogenesis. Diet restriction also reduced the risk of prostate cancer. Tomato phytochemicals and diet restriction may act by independent mechanisms.

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