原位膀胱癌大鼠建模方法比较及超声鉴定方法

目的通过对大鼠分别给予N-正丁基-N-(4-羟基-丁基)亚硝胺[N-butyl-N-(4-hydroxybutyl)nitrosamine,BBN]饮水饲养和N-甲基亚硝基脲(N-methyl-nitrosourea,MNU)膀胱灌注,来比较两种方法的造模效果以及各自的优缺点。判断B型高频超声对大鼠原位膀胱癌的诊断价值。方法BBN组大鼠给予0.05%的BBN溶液连续喂养6周,后更换为2%的枸橼酸钠溶液连续喂养22周,第28周末为诱导终点。MNU组大鼠给予MNU溶液(20mg/ml)膀胱灌注,每两周1次,每次0.1ml/只,连续灌注8周,后再常规喂养6周,第14周为诱癌终点。分别于第28周末(BBN组)和第14周末(MNU组)对两组大鼠进行超声扫描诊断,并在处死后取膀胱组织行病理学观察。比较两组的存活率和存活成瘤率。结果 BBN诱癌组20只大鼠28周后存活11只,成瘤8只,存活率为55%,存活成瘤率为72.7%。MNU组20只大鼠14周后存活18只,成瘤17只,存活率为90%,存活成瘤率为94.4%。结论利用MNU膀胱灌注行大鼠膀胱癌造模,其存活率和存活成瘤率均显著高于BBN饮水饲养造模。超声可作为大鼠膀胱癌造模活体检测的可靠方法。     

两种构建大鼠膀胱癌模型方法的比较研究

目的:通过N-正丁基-N-(4-羟基-丁基)亚硝胺[N-butly-N-(4-hydroxybutyl)nitrosamine,BBN](BBN)喂饲和MNU膀胱灌注方法构建大鼠膀胱癌模型,比较两种实验方法的优缺点.方法:BBN诱癌组大鼠使用0.05% BBN溶液连续喂养六周.后改用2%枸橼酸钠溶液作后续喂养22周,第28周为诱导的终点.MNU诱癌组大鼠行MNU膀胱灌注,每两周灌药1次,每次2 mg/只.共4次.第10周为诱导的终点.比较两组大鼠的成瘤率和死亡率.结果:BBN诱癌组30只大鼠喂养28周后存活16只,11只成瘤,死亡率46.7%,存活大鼠成瘤率68.8%;MNU诱癌组30只大鼠第10周存活28只,25只成瘤,死亡率6.7%,存活大鼠成瘤率89.3%.结论:利用MNU行大鼠膀胱灌注的方法构建大鼠膀胱癌模型,具有成瘤时间短、成瘤率高、大鼠死亡率低等特点,优于BBN喂饲大鼠成瘤的方法.     

γ-亚麻酸膀胱灌注治疗大鼠膀胱癌的实验研究

为了探讨γ-亚麻酸诱导大鼠膀胱癌细胞凋亡的机制,我们采用γ-亚麻酸对膀胱癌荷瘤大鼠行膀胱灌注,观察灌注前后肿瘤细胞中丙二醛(MDA)浓度的变化,增殖细胞核抗原(PCNA)以及Fas和FasL的表达情况,现报告如下. 材料与方法 8～10周龄SPF级雌性SD大鼠60只,体质量250～300 g,由上海斯莱克实验动物有限责任公司提供.应用N-甲基亚硝基脲(MNU,美国Sigma公司)膀胱灌注,9周后诱导出大鼠膀胱癌动物模型[1].1％戊巴比妥钠腹腔内注射麻醉,手术切取部分膀胱癌组织,缝合膀胱.术后1周,60只大鼠随机分为2组,每组30只.实验组:膀胱灌注浓度为2.5 mg/ml的γ-亚麻酸(美国Sigma公司),每只每次用量0.4 ml(1mg/次),保留2h.隔日1次,共3次.     

大鼠原位膀胱癌模型的建立及CT鉴定方法

目的研究N-甲基亚硝基脲(N-methyl-nitrosourea,MNU)诱导大鼠原位膀胱癌模型的建立及CT鉴定方法。方法 50只SD大鼠随机分为两组,对照组(A组)15只,实验组(B组)35只。A组大鼠经尿道膀胱内灌注生理盐水,每两周一次,每次0.1ml,共4次。B组大鼠用MNU以同样的方法灌注,每次0.2mg。于第14周末对两组大鼠进行膀胱CT扫描诊断,并且处死后取膀胱组织行病理学观察。结果A组13只大鼠经CT扫描未发现膀胱肿瘤,病理检查未见肿瘤组织。B组28只大鼠CT扫描膀胱均见明显异常,表现为膀胱壁局部肿块突起或不规则增厚、密度不均,病理诊断均为膀胱癌。结论MNU诱导大鼠原位膀胱癌模型是一种较为简单、可靠的建模方法。活体大鼠膀胱CT扫描与病理学结果有高度一致性,可作为该模型的活体鉴定方法。     

吡柔比星灌注对大鼠膀胱癌生长的抑制作用

目的探讨吡柔比星膀胱灌注对大鼠膀胱肿瘤生长的抑制作用和机制。方法将40只雌性Wistar大鼠,随机分为对照组(n=20)和吡柔比星组(n=20),制作N-甲基亚硝基脲诱导大鼠原位膀胱癌模型,于第8周分别行生理盐水和吡柔比星连续膀胱灌注,每周1次,共6次。于第14周进行病理观察、测量膀胱总重量,微血管密度(MVD)和凋亡指数(AI)。结果第14周时,对照组(n=16)和吡柔比星组(n=12)大鼠膀胱均可见明显肿物,光镜下可见癌组织侵入肌层。吡柔比星组大鼠膀胱的重量和肿瘤的MVD小于对照组(p<0.01);吡柔比星组大鼠膀胱肿瘤的AI大于对照组(p<0.01)。结论吡柔比星膀胱灌注可抑制大鼠膀胱肿瘤生长,可能与抑制肿瘤血管生长和诱导肿瘤细胞凋亡有关。     

2μm激光联合丝裂霉素治疗表浅性膀胱癌的疗效分析

目的 探讨2μm激光联合丝裂霉素治疗表浅性膀胱癌的安全性和有效性.方法 自2009年6月至2012年6月共116例表浅性膀胱癌患者入选研究,平均年龄58.3岁.其中,高级别泌尿上皮乳头状癌18例,低级别泌尿上皮乳头状癌93例,低度恶性倾向泌尿上皮乳头状瘤5例.影像学检查包括盆腔CT和排泄性尿路造影均显示没有膀胱外侵犯,淋巴结转移以及上尿路肿瘤性病变.所有患者在连续硬膜外麻醉下行2μm激光肿瘤切除,术后24h内即刻灌注撕裂霉素一次,然后1周后开始连续8周每周膀胱灌注丝裂霉素一次,然后改为每月一次维持治疗12个月.结果 116例患者总共201个肿瘤应用2μm激光成功切除,每例患者平均手术时间28min.没有出现闭孔神经反射或膀胱穿孔等严重并发症.所有患者均进行了12个月的膀胱灌注化疗.平均随访时间21.3个月,复发率为9.5％.结论 2μm激光联合丝裂霉素治疗表浅性膀胱癌是安全有效的.     

表阿霉素加卡介苗膀胱灌注预防膀胱癌术后复发的疗效观察

目的　探讨联合应用表阿霉素 (EPI)和卡介苗 (BCG)膀胱腔内灌注对预防膀胱癌术后复发的疗效。　方法　 4 4例膀胱乳头状移行细胞癌患者行经尿道电切术 (TURBT)或膀胱部分切除术后分为两组 :①EPI加BCG组 (2 4例 ) :术后 1周内单次EPI膀胱腔内灌注 ,第 2周后开始定期BCG膀胱腔内灌注。②单用BCG组 (2 0例 ) :术后 1周内开始单用BCG定期膀胱腔内灌注治疗。定期膀胱镜检查、尿细胞学检查和随访。　结果　 4 4例术后随访 2 4个月 ,单用BCG组 3例分别于术后 5、9、12个月复发 ,复发率 15 % (3/ 2 0 )。EPI加BCG组未见复发 ,χ2 检验 ,P <0 .0 5。两组均无严重药物反应和并发症。　结论　EPI早期单次膀胱内灌注加BCG定期膀胱内灌注的免疫化学疗法对预防膀胱乳头状移行细胞癌术后复发疗效肯定 ,毒副反应不明显 ,有较高的临床应用价值。     

B7-H1 与B7-H4 在膀胱癌大鼠及其癌旁组织中的差异表达

目的:研究膀胱原位癌组织及癌旁组织中共刺激分子 B7-H1与 B7-H4的表达情况,并分析二者的相关性。方法:采用 N-亚硝基 -N-甲基脲(MNU)溶液膀胱灌注法制备膀胱癌大鼠模型(30只),处死大鼠,获取癌组织及癌旁组织,进行病理检查;采用生理盐水溶液膀胱灌注法作为对照组( 12只),处死大鼠,获取膀胱组织,进行病理学检查;采用 RT-PCR技术分别检测对照组大鼠膀胱组织( A组)、膀胱癌模型组癌组织( B组)及模型组癌旁组织( C组)中 B7-H1与 B7-H4的 mRNA的表达水平,并分析二者之间的相关性。结果: 30只膀胱癌模型组大鼠, 28只模型制备成功,造模成功率 93.3%。A组、C组 B7-H1、B7-H4 mRNA表达量均明显低于 B组(0.71±0.38、0.79±0.21 vs 1.44±0.67;0.84±0.22、     

关木通对大鼠的致肿瘤作用及丹参的干预

目的：观察丹参对马兜铃酸诱导的大鼠胃及膀胱肿瘤病变的影响。方法：给大鼠灌服关木通浸膏（含马兜铃酸10mg·kg^-1·d^-1）12～24周,并给予不同剂量丹参水溶液（5、10、15g·kg^-1·d^-1）,于实验第12、16、20、24周处死大鼠,留取胃、膀胱及肾脏标本,观察其病理学改变。结果：实验第12周开始,所有马兜铃酸诱导的大鼠前胃均出现不同程度的病理改变,胃黏膜可见乳头状增生或乳头状瘤,并伴有上皮轻-重度异型增生,以模型组病变明显,并随实验进展而程度加重、范围扩大,出现原位癌病变。模型组大鼠膀胱黏膜内可见乳头状增生或乳头状瘤,至实验第24周,病变加重,可见多发性乳头状瘤伴局灶上皮异型增生,并有淋巴细胞浸润,部分大鼠膀胱组织表现为高分化原位癌。丹参干预后胃及膀胱病变有所减轻。马兜铃酸诱导的大鼠肾组织主要表现为肾小管间质病变,未出现癌变表现。结论：丹参干预后可减轻马兜铃酸诱导的大鼠胃组织及膀胱病变,具有一定的抗肿瘤作用。     

PI3-K抑制剂LY294002增强丝裂霉素C对大鼠原位膀胱癌抑制作用的研究

目的 研究PI3-K抑制剂LY294002在大鼠体内应用时对膀胱灌注化疗药物丝裂霉素C(mitomycin C,MMC)的协同抑癌作用以及毒副作用.方法 对荷原位膀胱癌的大鼠进行膀胱内灌注生理盐水、MMC、LY294002,记录大鼠体重变化、CT动态观察膀胱肿瘤变化、处死后直接测量膀胱肿瘤大小及观察灌注治疗完成后的存活率.结果 MMC联合LY294002灌注治疗4周后,荷膀胱癌大鼠平均体重明显高于单独MMC治疗组,CT扫描显示MMC联合LY294002灌注治疗对膀胱肿瘤的抑制作用强于单独MMC灌注.MMC联合LY294002灌注治疗4周后,大鼠膀胱内肿瘤直径小于单独MMC灌注组.灌注治疗4周后,各组大鼠存活率差异无统计学意义.LY294002灌注治疗会导致大鼠一过性的体重下降,无其他严重不良反应发生.结论 LY294002能增强MMC对大鼠膀胱癌的抑制作用,LY294002在大鼠体内应用时无严重不良反应发生.     

N-甲基亚硝基脲的制备及其诱发膀胱肿瘤的作用

目的 研究Ｎ－甲基亚硝基脲（ＭＮＵ）制备方法及其诱发大白鼠膀胱肿瘤的作用。方法 由甲胺盐酸盐合成诱癌剂ＭＮＵ,进行大白鼠膀胱灌注２ｍｇ／次,每２周１次,共４次,以光镜、扫描电镜、透射电镜等为观察手段,对其诱发的膀胱肿瘤进行观察。结果 ８周诱发膀胱肿瘤率为１００％,其组织学检查及病理学特征与人膀胱肿瘤十分相似。结论 自制的ＭＮＵ诱发的大白鼠膀胱肿瘤为比较理想的动物模型。     

Effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in a rat bladder tumor model

BackgroundInvestigate the effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in rat bladder tumor models.MethodsThe bladder tumor model of 75 specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats aged 5–6 weeks was established by n-methyl-N-nitrosourea (MNU) bladder perfusion induction, and the model rats were randomly divided into model group, low-dose (L-dose) group, medium-dose (M-dose) group, high-dose (H-dose) group, and positive drug (hydroxycamptothecine, HCPT) group. L-dose group, M-dose group, and H-dose group were treated with 5 g/kg, 10 g/kg, and 20 g/kg, respectively. The HCPT group was treated with 2 mg/kg hydroxycamptothecin at 1 mL/kg once a week and the model group were treated with the same amount of normal saline for 4 weeks. The quality of bladder cancer tissues in each group was measured. The pathological changes and microvascular density of bladder tissues were observed, and the apoptosis rate of vascular endothelial growth factor (VEGF), tumor tissue and the protein expression levels of factor associated suicide (Fas), factor associated suicide ligand (FasL) and Caspase3 in bladder tissues were detected.ResultsBladder cancer was induced 14 weeks after initial bladder perfusion with MNU. In the model group, epithelial cells of bladder tissue showed atypically hyperplasia with various sizes and disorders. After treatment with Stellera chamaejasme, the hematoxylin-eosin (HE) scores, bladder weight, microvascular density, and VEGF were significantly decreased, and the tumor inhibition rate, cell apoptosis, and the expression of apoptosis-related proteins Fas, FasL, and Caspase3 were significantly increased in the bladder tissue. The above changes were dose-dependent with Stellera chamaejasme.ConclusionsMNU can be used to prepare a rat bladder cancer model. Stellera chamaejasme has a good therapeutic effect on rat bladder cancer, which may inhibit the progression of bladder cancer by inhibiting micro-angiogenesis and inducing the apoptosis of bladder tumor cells.     

The effect of sex hormones on the incidence of experimental urinary bladder tumors in rats (author's transl)]

A study was conducted of the effects of testosterone propionate, estradiol and estriol on experimental bladder tumors induced in 8-week old Wistar-Imamichi strain male rats by oral administration of 0.02 mg/head/day of N-butyl-N-(4-hydroxybutyl)-nitrosamine as carcinogen for 8 weeks. In the group of rats which was not treated for 12 weeks after completion of the carcinogen administration, 6 of 25 cases showed bladder tumors and 2 of 25 showed hyperplasia. In the group of rats which was injected intramuscularly 3 mg/kg (body weight) of testosterone priopionate 1 time weekly from the beginning of carcinogen administration through the 20th week, 9 of 20 cases showed bladder tumors and 2 were with hyperplasia. In the group of rats which was injected intramuscularly 3 mg/kg (body weight) of estradiol 1 time weekly from the beginning of the carcinogen administration through the 20th week, 2 of 23 cases developed bladder tumors and 5 were with hyperplasia. (Author's, modified)     

Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases

Noninvasive squamous lesions are distinctively uncommon in biopsies of the urinary bladder with the exception of nonkeratinizing squamous metaplasia. The clinical significance of these squamous lesions in the bladder remains to be explored. A total of 29 cases of transurethral biopsies and resections of the bladder containing noninvasive squamous lesions (excluding nonkeratinizing metaplasia) were studied from the consult files of one of the authors. These cases included keratinizing squamous metaplasia (5), verrucous squamous hyperplasia (5), squamous papilloma (5), condyloma acuminatum (3), and squamous cell carcinoma in situ (CIS) (11). Immunohistochemistry for epithelial growth factor receptor (EGFR) and in situ hybridization for wide-range human papillomavirus was performed on 23 cases. The follow-up period ranged from 2 months to 3 years with an average of 1.5 years. After the initial diagnoses in biopsies of the bladder, 10 patients received cystectomies, and 7 patients received repeat tissue sampling of the bladder. Of the 5 patients with keratinizing squamous metaplasia, 2 patients had invasive urothelial carcinoma with squamous features in their cystectomy specimens at intervals of 3 and 14 months, respectively, 1 had persistent keratinizing squamous metaplasia on rebiopsy. Of the 5 patients with verrucous squamous hyperplasia, 1 patient had invasive squamous cell carcinoma at cystectomy at an interval of 14 months, 1 had squamous cell CIS on rebiopsy, 1 had persistent verrucous squamous hyperplasia on rebiopsy, and 2 had no evidence of disease at 6 and 24 months. Of the 5 patients with squamous papilloma, 1 patient had low-grade urothelial carcinoma at cystectomy at an interval of 21 months (h/o low-grade urothelial carcinoma preceding papilloma diagnosis), 2 were free of lesions at rebiopsy. Of the 3 patients with condyloma acuminatum, 1 had squamous CIS at cystectomy at an interval of 3 months, 1 had invasive squamous cell carcinoma at 20 months. Of the 11 patients with squamous cell carcinoma in situ (CIS), 3 patients had invasive squamous cell carcinoma at intervals of 2, 3, and 4 months, respectively, 1 had invasive urothelial carcinoma with squamous features in cystectomies at an interval of 12 months, 1 had squamous cell CIS at 10 months, 1 had high-grade urothelial carcinoma (not otherwise specified) at rebiopsy at an interval of 6 months, and 1 had no evidence of disease at 8 months. Among the 9 patients with invasive carcinoma, 4 patients died in the period of 0.5 to 3 years after the diagnoses. Immunohistochemical study with EGFR demonstrated strong signals in 20 cases and no signals in 2 cases. Wide-range human papillomavirus DNA signal was detected in 1 case of condyloma acuminatum and 1 case of squamous cell CIS. Keratinizing squamous metaplasia, verrucous squamous hyperplasia, and condyloma acuminatum in the urinary bladder can be associated with subsequent or concurrent in situ, or invasive squamous carcinoma and should be closely followed. Squamous cell CIS in the urinary bladder is often associated with subsequent or concurrent invasive carcinoma with squamous differentiation. Enhanced expression of EGFR in these bladder squamous lesions suggests that EGFR may represent a logic therapeutic target in those squamous lesions that are difficult to manage clinically.     

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.     

Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model

A rodent bladder cancer model that is induced by intravesical instillation of N-methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU and were sacrificed at various intervals. By week 13 all animals had flat atypia and/or papillary transitional cell tumors, and 67% of the lesions were moderately (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle invasive tumors that eventually killed the host. A cohort of 40 MNU treated animals was subsequently treated commencing at week 17 after initiation of MNU with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin. There was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17. A second cohort of 107 animals commenced therapy at 13 weeks after initiation of MNU with one of five intravesical six week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however, BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression. In conclusion, this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons: 1) it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in-situ that progress to muscle invasion and kill the host; 2) as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large; however, tumor growth is inhibited when treated early; and 3) this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer.     

尿路上皮内翻性乳头状瘤62例临床分析

目的 探讨尿路上皮内翻性乳头状瘤的临床表现、生物学行为及临床诊治方案.方法 回顾性分析1990年1月至2008年8月62例尿路上皮内翻性乳头状瘤患者的临床资料.男性51例,女性11例,平均年龄56.4岁.单发56例,多发6例.肉眼血尿为最常见的首发临床表现.发病部位在输尿管5例,4例行肿瘤局部切除术,1例行左肾及输尿管全长切除术;发生于输尿管合并膀胱1例,行膀胱全切术;发生于膀胱52例,44例行经尿道膀胱肿瘤切除术,6例行膀胱部分切除术,2例行膀胱全切术;发生于尿道4例,1例行经尿道肿瘤切除术,3例行尿道肿瘤切除术.结果 62例患者术后病理均证实为内翻性乳头状瘤,其中伴发尿路上皮癌7例.49例随访3个月～12年.2例分别于术后7和79个月复发,3例分别在术后18个月、2年和6年发现尿路上皮癌.结论 尿路上皮内翻性乳头状瘤为良性肿瘤,需与尿路上皮恶性肿瘤相鉴别.手术是其主要治疗方式,术后应定期复查膀胱镜及随访.     

A study of BBN induced bladder cancer in mice. The time differences in changes of histopathology and nuclear DNA content

To evaluate the process of tumor progression in BBN induced bladder cancer, BBN was administered to C57BL/6 mice for 10 weeks. The mice were sacrificed every week from the 5th week to the 22nd week. The urinary bladder was embedded in paraffin block for histopathological examination and was sampled for DNA content analysis by flow cytometry. The results were as follows: 1. In the histopathological findings, the incidence of atypical hyperplasia of the urinary bladder, indicative of a precancerous state, was 29% 7 weeks after the initiation with BBN. And the cancer was found in 74% of the mice 9 weeks after the initiation. 2. In the analysis of nuclear DNA content, the atypical hyperplasia and the incipient cancer of the urinary bladder were all DNA diploid, and the DNA aneuploid was found in 50% of the cancer group 11 weeks after the initiation. 3. These data suggest that the change of nuclear DNA content is an occurrence after the completion of the carcinogenesis in BBN induced bladder cancer of mice.     

Effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N- (4-hydroxybutyl) nitrosamine.

We recently reported fleroxacin significantly affected cell proliferation in a dose-dependent manner in transitional cell carcinoma cell lines. In this study, we investigated the effect of fleroxacin on mouse bladder carcinogenesis with N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN). Five-week-old C57BL/6 female mice were divided into three groups. The forced oral administrations of fleroxacin (10 or 50 mg/kg/day) were done for 1 week, then the 0.05% BHBN was given for 8 or 12 weeks. Fleroxacin treatments were continued until sacrifice. The mice were sacrificed at 4 weeks or 8 weeks latent period after BHBN administration, and the histological changes in the bladder were examined. Our study suggested that fleroxacin tended to suppress the development of bladder carcinoma or the malignant changes induced by a shorter period of BHBN administration (8 weeks) in mice. However, in the group of the BHBN administration for 12 weeks, there were no significant effects on the prevention of bladder carcinoma in both of the treatment groups with fleroxacin (10 or 50 mg/kg/day). This study did not make it clear that oral administration of fleroxacin suppressed the development of bladder carcinoma induced by BHBN in mice. However, it is very preliminary data and further experiments need to be done with a much higher dose of the fleroxacin or with other kinds of fluoroquinolone antibiotics.