Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets
Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets
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DOI：
10.1093/jnci/djg081
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发表时间：
2003-11-05
影响因子：
10.3
通讯作者：
Clinton, SK
中科院分区：
文献类型：
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作者：
Boileau, TWM;Liao, ZM;Clinton, SK
背景：番茄制品或番茄红素的摄入和能量限制被认为可以降低人类前列腺癌的风险。我们研究了这些饮食变量在大鼠前列腺癌模型中的作用。研究方法：用N-甲基-N-亚硝基脲和睾酮处理以诱导前列腺癌的雄性大鼠（n = 194）喂食含有全番茄粉（13 mg番茄红素/kg饮食）、番茄红素珠粒（161 mg番茄红素/kg饮食）或对照珠粒的饮食。每组大鼠随机分为自由采食组和20%限食组。用对数秩检验检验饮食组成或限制的Kaplan-Meier生存曲线之间的差异。考克斯比例风险模型被开发来检查饮食组成和限制对存活率的联合作用。统计检验是双侧的。结果如下：喂食番茄粉饮食的大鼠前列腺癌死亡风险低于喂食对照微珠的大鼠（风险比[HR] = 0.74，95%置信区间[CI] = 0.59至0.93; P = 0.009）。相比之下，对照组和喂食甘草酸的大鼠的前列腺癌特异性死亡率相似（P = 0.63）。对照组、番茄红素组和番茄粉组大鼠死于前列腺癌的比例分别为80%（95%CI = 68%~ 89%）、72%（95%CI = 60%~ 83%）和62%（95%CI = 48%~ 75%）。饮食限制组大鼠的无前列腺癌生存期长于自由进食组大鼠（HR = 0.68，95% CI = 0.49至0.96; P = 0.029）。自由采食大鼠中发生前列腺癌的大鼠比例为79%（95% CI 69%-86%），限食大鼠中为65%（95% CI 54%-74%）。饮食组成和饮食限制之间没有观察到相互作用。结论：食用番茄粉而不是番茄红素可抑制前列腺癌的发生，这表明番茄制品中除了番茄红素外还含有可改变前列腺癌发生的化合物。饮食限制也降低了患前列腺癌的风险。番茄植物化学物质和饮食限制可能通过独立的机制起作用。
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.