Masuda C, Wanibuchi H, Sekine K, Yano Y, Otani S, Kishimoto T, Tsuda H, Fukushima S
Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Jpn J Cancer Res. 2000 Jun;91(6):582-8. doi: 10.1111/j.1349-7006.2000.tb00985.x.
Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.
初乳中高浓度存在的牛乳铁蛋白（bLF）对大鼠膀胱癌发生的化学预防作用，通过大鼠膀胱中期生物测定法进行了研究。在实验1中，将总共80只6周龄的F344雄性大鼠分为5组。第1组和第2组在饮用水中给予0.05%的N-丁基-N-（4-羟基丁基）亚硝胺（BBN），持续8周，间隔1周后，分别给予2%和0.2%的bLF进行饮食补充。第3组接受0.05%的BBN处理8周，然后不进行任何处理。第4组从第9周开始单独给予2%的bLF，之前未接触过致癌物。第5组在整个实验过程中不进行任何处理。所有大鼠在第36周结束时处死。与第3组相比，第1组膀胱肿瘤（癌和乳头状瘤）的多发性显著降低。与第3组相比，第1组和第2组膀胱肿瘤的最大切面面积也显著减小。第4组和第5组未观察到膀胱肿瘤。在实验2中，将总共60只大鼠分为两组（每组30只）；两组均用0.05%的BBN处理4周，间隔1周后，一组接受2%的bLF（第1组），另一组接受基础饮食（第2组），持续4周。第1组显示5-溴-2'-脱氧尿苷（BrdU）标记指数有下降趋势。通过ELISA以及蛋白质免疫印迹分析在喂食bLF的大鼠尿液中检测到了bLF。研究结果表明，2%的bLF可以抑制BBN诱导的大鼠膀胱癌发生，这可能是由于尿液中的bLF所致。
