URINARY BLADDER CANCER PROMOTION BY DIETARY L-TRYPTOPHAN

过量促进膀胱癌发生的研究进展 饮食中的L-色氨酸和维生素B6缺乏症将使用 以N-(4-(5-硝基-2-呋喃)-2-噻唑基)甲酰胺(FANFT)为引发剂。这个 膳食L-色氨酸及其代谢产物在膀胱癌发病中的作用 目前还不清楚。早期研究报告DL-色氨酸是一种共同致癌物质 动物模型，但未能显示单独喂养色氨酸的致癌作用。 科恩博士已经证明了DL-色氨酸是一种膀胱增强剂 以0.2%FANFT喂养6周开始致癌。膀胱癌产生 单纯FANFT组为20%，FANFT加2%组为50%-53% DL-色氨酸组。进一步的研究使用了较低剂量的致癌物质(4 周)和2%L-色氨酸来评价色氨酸的促进作用。 尽管单纯FANFT组的肿瘤产率很低(4%)，但增加 FANFT加色氨酸组(19%)差异无统计学意义。维生素B6 (磷酸吡哆醛)密切参与色氨酸代谢和 纠正了膀胱色氨酸代谢的异常模式 癌症患者。一项早期的动物研究表明，维生素B6 补虚能提高膀胱癌的产率。我们建议用4周的时间 FANFT作为男性膀胱癌启动剂的治疗 Fischer大鼠及L色氨酸过量和维生素B6(吡哆醇)的研究 缺乏作为推动者的作用。1)将使用以下方法重复先前的研究 更多的动物数量，以确保统计上有意义的结果。2) 维生素B6缺乏，导致色氨酸代谢异常 排泄模式，将在这个模型中单独评估。3)维生素B6 虚实结合L-色氨酸过剩进行评估以确定 如果这两种情况在促进膀胱癌方面相互加强。 4)尿色氨酸代谢产物用高压液体测定 所有生物测试中的层析，以指示哪些评估是最好的 与膀胱癌的发生密切相关。5)放射自显影和扫描 电子显微镜研究将评估这些饮食的效果 膀胱增生症的手法治疗。建议进行的研究包括 重要是因为L-色氨酸及其代谢物是内源性的 正常尿液中的物质，并可能有助于显著促进 人类膀胱癌的活动性。

Studies on the promotion of urinary bladder carcinogenesis by excess dietary L-tryptophan and a Vitamin B6 deficiency will be conducted using N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide (FANFT) as the initiator. The role of dietary L-tryptophan and its metabolites in urinary bladder cancer is unclear. Early studies reported DL-tryptophan as a co-carcinogen in animal models but failed to show carcinogenicity of tryptophan fed alone. Dr. S. M. Cohen has demonstrated DL-tryptophan as an enhancer of bladder cancer initiated by feeding 0.2% FANFT for 6 weeks. Bladder tumor yields were 20% in the FANFT alone group and 50-53% in the FANFT plus 2% DL-tryptophan group. Further studies used a lower dose of carcinogen (4 weeks) and 2% L-tryptophan to evaluate a promotional role of tryptophan. Although the tumor yield was low in the FANFT alone group (4%) the increase in the FANFT plus tryptophan group (19%) was not significant. Vitamin B6 (pyridoxal phosphate) is intimately involved in tryptophan metabolism and has corrected abnormal tryptophan metabolite patterns in urinary bladder cancer patients. An early animal study suggested that Vitamin B6 deficiency enhanced the bladder tumor yield. We propose to use the 4-week treatment with FANFT as the initiator of urinary bladder cancer in male Fischer rats and to study L-tryptophan excess and Vitamin B6 (pyridoxine) deficiency as promoters. 1) The earlier study will be repeated using larger numbers of animals to secure statistically significant results. 2) Vitamin B6 deficiency, which causes abnormal tryptophan metabolite excretion patterns, will be evaluated alone in this model. 3) Vitamin B6 deficiency combined with L-tryptophan excess will be assessed to determine if these two conditions potentiate each other in bladder cancer promotion. 4) Urinary tryptophan metabolites will be measured by high pressure liquid chromatography in all bioassays to indicate which evaluations are best correlated with bladder cancer promotion. 5) Autoradiographic and scanning electron microscopic studies will evaluate the effects of these dietary manipulations on urinary bladder hyperplasia. The proposed studies are important because L-tryptophan and its metabolites are endogenous substances in normal urine and could contribute significant promoting activity in human urinary bladder cancer.