二甲基苯蒽诱发大鼠乳腺癌的组织形态学和微血管密度观察

目的:研究诱发性大鼠乳腺癌发生过程中组织形态学变化和肿瘤微血管密度(MVD).方法:Wistar雌性大鼠85只,SD雌性大鼠22只,配制浓度为10 mg/ml的二甲基苯蒽(DMBA)麻油溶液灌胃大鼠.17只大鼠8周前死亡,剩余90只大鼠从第8周开始至24周,每2周取大鼠10只活杀,观察乳腺外形,取乳腺肿块HE染色和Ⅷ因子相关抗原免疫组化染色.结果:存活8周以上的90只大鼠中,73只成功诱发乳腺肿瘤,其中乳腺良性增生11只,乳腺癌62只.乳腺癌62只大鼠中,浸润性导管癌35只,浸润性小叶癌15只,乳头状腺癌5只,其他类型肿瘤7只.乳腺癌分化程度分级为:高分化5只,中分化36只,低分化21只.乳腺癌MVD平均值为(6.53±2.71)个/高倍视野,乳腺良性增生MVD为(1.67±0.95)个/高倍视野,乳腺癌MVD显著高于乳腺增生性疾病(P<0.01).低分化乳腺癌MVD显著高于中、高分化乳腺癌(P<0.001).结论:DMBA灌胃Wistar雌性大鼠乳腺癌诱发成功率高,肿瘤分化程度与微血管密度密切相关.     

二甲基苯蒽诱发大鼠乳腺癌的组织形态学和微血管密度观察

目的：研究诱发性大鼠乳腺癌发生过程中组织形态学变化和肿瘤微血管密度（MVD）。方法：Wistar雌性大鼠85只,SD雌性大鼠22只,配制浓度为10 mg/ml的二甲基苯蒽（DMBA）麻油溶液灌胃大鼠。17只大鼠8周前死亡,剩余90只大鼠从第8周开始至24周,每2周取大鼠10只活杀,观察乳腺外形,取乳腺肿块HE染色和Ⅷ因子相关抗原免疫组化染色。结果：存活8周以上的90只大鼠中,73只成功诱发乳腺肿瘤,其中乳腺良性增生11只,乳腺癌62只。乳腺癌62只大鼠中,浸润性导管癌35只,浸润性小叶癌15只,乳头状腺癌5只,其他类型肿瘤7只。乳腺癌分化程度分级为：高分化5只,中分化36只,低分化21只。乳腺癌MVD平均值为（6.53±2.71）个/高倍视野,乳腺良性增生MVD为（1.67±0.95）个/高倍视野,乳腺癌MVD显著高于乳腺增生性疾病（P〈0.01）。低分化乳腺癌MVD显著高于中、高分化乳腺癌（P〈0.001）。结论：DMBA灌胃Wistar雌性大鼠乳腺癌诱发成功率高,肿瘤分化程度与微血管密度密切相关。     

两种建立金黄地鼠颊囊癌模型方法的对照研究

目的二甲基苯并蒽丙酮注射法建立金黄地鼠颊囊癌动物模型,并与传统涂抹法相比较,为颊囊癌研究提供理想的动物模型。方法随机将81只金黄地鼠分为注射组、涂抹组和空白对照组。DMBA丙酮注射组60只地鼠,将注射浓度预设为0.5%、0.4%、0.3%、0.2%、0.1% 5个组,每组12只地鼠,每周两次,于注射后每周进行大体观察、监测体重并计算肿瘤生长率,至3、6、9、12周麻醉后各处死3只,进行组织学观察;涂抹组15只地鼠,以0.5% DMBA丙酮涂抹,每周三次,至6、9、12、15、18周后麻醉处死3只;空白对照组不做任何处理,于12周全部处死行组织学观察。结果注射浓度组04%、03%、0.2%、0.1% 分别在13,9,12,16周时出现约为0.8 cm×0.6 cm×0.5 cm大小的肿瘤;12周时成瘤率分别为25%、87%、42%、58%;死亡率分别为48%、11%、13%、10%;相比0.5% DMBA丙酮涂抹组,12周时成瘤率为48%,死亡率为37%,至18周时才出现颊黏膜高分化鳞癌。结论经筛选采用03% DMBA丙酮液注射法可诱发形成口腔鳞癌动物模型,缩短建模周期,降低建模成本,能为科学研究提供较为理想的动物模型。     

家兔颊黏膜鳞状上皮癌前病变模型制备及癌前病变逆转研究

目的探讨家兔口腔颊黏膜鳞状上皮癌前病变动物模型的建立及癌前病变的逆转方法。方法将二甲基苯并蒽(DMBA)制成DMBA丙酮溶液及DMBA药膜，涂抹或贴附于家兔口腔颊黏膜，3次倜，共12周。癌前病变模型制成后，再贴全反式维甲酸(ATRA)药膜，3次倜，共12周，观察其转归。颊黏膜标本进行病理组织学检查，同时扫描及透射电镜超微结构观察。结果家兔颊黏膜应用DMBA12周后均出现不典型增生，其中Ⅱ～Ⅲ级不典型增生发生率为78．5％(11／14)。应用全反式维甲酸12周后，颊黏膜癌前病变不同程度地逆转。结论应用DMBA可成功构建家兔口腔颊黏膜鳞状上皮癌前病变模型，贴膜法是1种比较好局部给药方法；ATRA可能对鳞状上皮不典型增生具有一定的逆转作用。     

市场牛奶和传统牛奶对乳腺癌发生影响的研究

目的:评价市场牛奶和传统牛奶对二甲基苯并蒽(DMBA)诱导的大鼠乳腺肿瘤发生的影响。方法:120只雌性大鼠采用致癌剂DMBA诱发乳腺癌后,将大鼠分为市场牛奶组(C)、内蒙古黄牛奶组(T)和自来水组(W),比较3组大鼠的乳腺肿瘤发生率、发生时间和数量。结果:C组大鼠乳腺首发肿瘤出现最早(DMBA干预后的第5周),T和W组分别比C组晚1和2周;C组大鼠肿瘤发生的潜伏期〔(9.1±3.8)周〕短于T组〔(11.7±4.0)周〕;C、T和W组肿瘤发生率分别为80.0%(32/40)、80.0%(32/40)和52.5%(21/40);C组肿瘤发生的数量(142个)高于T组(92个)和W组(65个)。结论:目前,我国市场上销售的牛奶对DMBA诱导的大鼠乳腺肿瘤的发生具有促进作用,牛奶中的雌孕激素,特别是雌激素在促癌实验中发挥了关键作用。     

姜黄素对DMBA诱发的地鼠口腔癌预防作用

背景与目的:选用二甲基苯并蒽(7,12-dimethylbenz(a)anthracene,DMBA)诱发的金黄色地鼠口腔癌模型,进行了姜黄素对口腔癌的预防作用研究,并探讨其防癌机制。材料与方法:试验设阳性对照组(局部涂0.5%DMBA,每周3次,共14周)、二个姜黄素组(在涂DMBA2周前开始分别涂5μmol/L和10μmol/L姜黄素至14周实验结束)和阴性对照组(仅涂石蜡油)。结果:10μmol/L姜黄素处理显著降低了口腔肿瘤发病率和癌发病率,5μmol/L对肉眼肿瘤数目和体积、异常增生及癌数目的抑制分别降低了33.8%、36.3%、37.6%和29.0%。10μmol/L分别降低了46.0%、63.7%、44.7%和37.0%。此外,姜黄素处理均抑制了单纯增生和异常增生组织的微核形成和单纯增生、异常增生和癌组织的Brdu增殖指数。结论:姜黄素对DMBA诱发的地鼠口腔癌有预防作用,其机制与保护DNA损伤、抑制细胞增殖有关。     

大豆异黄酮干预雌性SD大鼠乳腺癌发生、发展的实验研究

目的:研究大豆异黄酮(soybean isoflavones, SOY)对二甲基苯蒽(7,12-dimethylbenz anthrancene,DMBA)诱导的不同生理阶段的SD大鼠乳腺肿瘤发生、发展的影响.方法:60只雌性SD大鼠分成幼鼠DMBA组、幼鼠DMBA+SOY组、成年鼠DMBA组和成年鼠DMBA+SOY组,观察各组大鼠乳腺癌的发病率、潜伏期和肿瘤大小;通过免疫组织化学法检测大鼠乳腺癌组织的核仁组成区嗜银蛋白(silver-stainning nucleolar organizer region,AgNOR)阳性细胞计数、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和C-erbB-2的表达.结果:幼鼠DMBA组和成年鼠DMBA组乳腺癌发病率分别为80.0%和40.0%(P＜0.05);幼鼠DMBA+SOY组乳腺癌发生的潜伏期明显长于幼鼠DMBA组(P=0.036);各组大鼠乳腺肿瘤大小无明显差异;幼鼠DMBA组AgNOR计数、PCNA和C-erbB-2的表达水平均高于幼鼠DMBA+SOY组和成年鼠DMBA组(P<0.05).成年鼠DMBA组和成年鼠DMBA+SOY组间的乳腺癌发病率、肿瘤大小以及肿瘤组织的AgNOR计数、PCNA和C-erbB-2的表达水平差异均无统计学意义(P>0.05).结论:DMBA对幼鼠的致癌作用明显强于成年鼠.食用SOY对SD大鼠乳腺癌的发生、发展具有一定的影响,且对幼鼠的作用大于成年鼠.     

二甲基苯蒽诱发大鼠乳腺癌的病理及淋巴管生成的研究

目的研究大鼠诱发性乳腺癌发生的病理组织学和淋巴管密度(LVD)的变化。方法 Wistar雌性大鼠96只,二甲基苯蒽(DMBA)麻油溶液灌胃。16只大鼠9周内死亡,存活10周以上80只。从第10周开始至24周,每2周取10只活杀,乳腺肿块HE染色、podoplanin相关抗原免疫组化染色和免疫荧光染色。结果 75只大鼠成功诱发乳腺肿块,其中乳腺良性增生16只,炎性肉芽肿2只,乳腺癌57只。乳腺癌和乳腺增生组织LVD平均值分别为(6.93±0.84)、(1.52±0.23)个/高倍视野,乳腺癌组织LVD显著高于乳腺增生组织(P<0.01)。高分化、中分化和低分化乳腺癌LVD分别为(4.43±0.68)、(5.83±1.03)和(9.48±0.93)个/高倍视野,低分化乳腺癌LVD显著高于中、高分化乳腺癌(P<0.001)。结论 DMBA灌胃Wistar雌性大鼠乳腺癌诱发成功率高,肿瘤淋巴管密度与肿瘤分化程度密切相关。     

已烯雌酚对Wistar大鼠乳腺癌发生的干预作用

背景与目的:作为一类人工合成雌激素药物,二乙基已烯雌酚(diethyl-stilbestrol,DES)被广泛应用于治疗雌激素不足所致的更年期综合征及骨质疏松症等,但其对乳腺上皮细胞作用的研究有待进一步探讨.本研究通过建立与人相似的Wistar大鼠乳腺癌发生的模型,并用DES进行干预,观察DES在Wistar大鼠乳腺癌发生过程中的作用.方法:利用不同剂量的DES干预二甲基苯蒽[7,12-dimethylben(a)anthracene,DMBA]诱导Wistar大鼠乳腺癌模型,研究其对乳腺上皮细胞的作用.实验分为6个组:对照组、DES1组、DMBA组、DES1 DMBA组、DES2 DMBA组和DES3 DMBA组,其中DES1、DES2和DES3中DES剂量分别为:0.1 mg·kg-1·d-1、0.2 mg·kg-1·-1和0.4 mg·kg-1·d-1喂养大鼠,观察44周处死大鼠,取乳腺组织作常规病理分析以及核仁组成区相关嗜银蛋白(silver-bindingnucleolar organizer regions,AgNOR)计数、PCNA染色强度指数(proliferating cell nuclear antigen staining intensity index,PCNA SⅡ)、Bcl-2和C-erbB-2蛋白表达测定.结果:DMBA组和DES1 DMBA组分别有13只和2只Wistar大鼠发生癌变;单纯DES1组大鼠乳腺上皮细胞AgNOR计数及PCNASⅡ水平上升,Bcl-2及C-erbB-2的表达提高,但未导致癌变;与其他组相比,DES2 DMBA组大鼠乳腺上皮细胞的AgNOR计数和PCNA SⅡ水平下降,Bcl-2及C-erbB-2的表达降低(P＜0.05);DES3 DMBA组上述指标与DES1 DMBA组差异无统计学意义(P＞0.05).结论:单纯小剂量DES可导致大鼠乳腺上皮细胞增生,但不导致乳腺组织癌变;在DMBA诱发大鼠乳腺上皮细胞癌变过程中,小剂量DES可以促使乳腺导管上皮细胞增生、乃至癌变;而中等剂量DES可以明显抑制大鼠乳腺上皮细胞增生,加大DES剂量,抑制作用不增强.     

DMBA诱发金黄地鼠颊囊癌的实验研究

目的：探讨二甲基苯并蒽(DMBA)诱发金黄地鼠颊囊癌后DNA含量的变化和细胞增殖情况。方法：金黄地鼠60只，随机分成6组，1—5组用0．5％DMBA涂擦双侧颊囊，分别于6周、8周、10周、12周、16周处死动物；正常对照组16周处死。切取颊囊标本每份标本分成两份，一份行组织学观察；另一份则行流式细胞仪检测，测定细胞DNA含量及细胞周期。结果：正常粘膜和单纯增生组细胞DNA均为二倍体(diploid)，轻、中度不典型增生有16．7％(2／12)异倍体出现；重度不典型增生则有33．3％(3／9)异倍体出现；原位癌有54．1％(6／11)异倍体出现；侵袭癌有78．57％(11／14)异倍体出现，且随颊粘膜病变加重，DI值及S期增殖率随之升高，重度不典型增生组S期细胞增殖率为最高，占39．31％。结论：DNA异倍体的出现是细胞恶性生物学行为的标志。S期细胞增殖率为恶性肿瘤增殖的指标，有利于对口腔癌的准确诊断，从而为临床口腔癌的治疗、预后评估提供有益的参考。     

Optimization of 7,12-dimethylbenz(a)anthracene-induced rat epithelial ovarian tumors

Ovarian carcinoma is the second most common malignant tumor of the female reproductive system and an notable cause of cancer death. The detection and diagnosis of early ovarian carcinomas are still clinical challenges, which calls for imaging studies using early ovarian carcinoma animal models. The present study aimed to optimize the 7,12-dimethylbenz(a)anthracene (DMBA)-induced model of rat ovarian tumors by investigating the delivery methods, induction dose and time of DMBA exposure, and explored the morphological features of tumors using MRI. Three schemes were performed. In scheme one the ovary was covered with absorbable hemostatic gauze loaded with a high concentration of liquid DMBA. For this scheme, 150 Sprague-Dawley rats were divided into three groups depending on the DMBA dose (1.0, 2.0 and 3.0 mg). In scheme two DMBA solution was injected under the ovarian capsule. For this scheme, 159 rats were divided into 0.5, 1.0 and 1.5 mg DMBA groups. In scheme three the ovary was covered with absorbable gauze loaded with a high concentration of solid DMBA. For this scheme 161 rats were divided into 1.0, 2.0 and 3.0 mg DMBA groups. Each group of the three schemes was further subdivided into 60-, 90-, 120-, 150- and 180-day groups. In scheme two, the tumor formation rate was 75.6% (99/131), which was the highest in the 1.5 mg group (86.4%, 38/44) and reached 100% (10/10) on day 120. The induced tumors were serous in 93.9% (93/99) of tumors. Borderline ovarian tumors accounted for 19.2% (19/99) of all tumors, and ovarian cancer accounted for 46.5% (46/99). The mean maximum diameter (MMD) of borderline ovarian tumors was 10.29±3.41 mm, and that of ovarian cancer was 15.19±7.10 mm. MMD of the solid components increased with increasing malignancy. Cystic, cystic-solid and solid tumors were observed. The ovarian subcapsular injection of 1.5 mg DMBA was the best scheme for the rat ovarian tumor model. The present model is ideal for investigating the occurrence, development and imaging of ovarian tumors.     

小鼠卵巢癌荷瘤动物模型的构建及其细胞系生物学特性分析

背景与目的:目前缺少可靠特异性早期发现卵巢癌,并防止复发和预防耐药的方法。良好的实验模型不仅可以很好地理解影响此疾病表型特征的生物遗传因素,还可以为干预策略的发展提供理论基础。本研究旨在构建小鼠的卵巢癌模型,建立卵巢癌细胞系,分析其生物学特性。方法:对8周龄的C57BL/6N×C3H/He杂交一代(F1)雌性小鼠,用剂量2.7Gy的252Cf的中子放射源给予全身放射线照射,诱导成卵巢癌后进行鼠间传代11次,取瘤组织体外分离培养瘤细胞并传代和建立肿瘤细胞系,应用细胞、分子生物学实验手段对建立的细胞系进行生物学特性检测。结果:经放射线照射成瘤的细胞在鼠间历时23个月传至第11代,皮下移植瘤存活率为100%,体外建立的细胞系OV99与阳性对照卵巢癌细胞系OVHM一样,在体外生长性能稳定。OV99细胞形态学和超微结构符合卵巢癌上皮组织基本特征;细胞含有76条染色体,呈端着丝粒,为鼠肿瘤细胞异常染色体;OV-99的细胞生长状态、细胞周期分布、癌基因p21、p185和抑癌基因p53的蛋白表达定量以及细胞周期蛋白PCNA和CyclinD,MHC表达量,和MAGE-1,MAGE-3mRNA表达等细胞生物学行为和OVHM的结果差异无显著性,但与鼠的正常卵巢组织中癌基因p21、p185和抑癌基因p53的蛋白表达定量以及细胞周期蛋白PCNA和CyclinD以及MHC表达量相比明显升高,MAGE-1、MAGE-3mRNA表达增强。结论:小鼠卵巢癌荷瘤模型及其细胞系OV99的建立为卵巢癌的研究提供了良好的实验材料。通过对OV99细胞的病理形态学、超微结构、染色体分布、细胞周期分布及不同肿瘤特征性基因等生物学行为分析,OV99符合卵巢癌细胞系的特征。     

兔肝Vx-2移植癌改良模型的建立

 目的 培养、建立稳定的兔肝Vx|2移植癌模型，探讨不同植瘤方式的成功率。方法 60只新西兰白兔随机分3组，每组20只。 分别以不同的方式将Vx|2瘤细胞植入兔的肝脏。观察：1.不同方式植瘤的成活率；2.B超测定肝内肿瘤7d、10d、14d、17d、21d时的大小，并计算肿瘤生长率；3.大体及镜下(光镜和电镜)瘤组织形态特征。结果 1.三组植瘤成活率分别为7/20、10/20、19/20，改良组植瘤成活率最高（P<0.05)，瘤体呈指数性生长；2.病理学及CT表明该瘤在肝组织中呈浸润式生长，其性状与移植于兔其它部位的Vx|2鳞状细胞癌特征相似。结论 成功建立了兔肝Vx|2移植癌模型，瘤组织块种植方式成功率明显高于其它两组方式，为肝癌介入治疗的基础及临床研究，提供了成熟的大型实验动物模型。     

Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture

Human ovarian cancer is predominantly of epithelial cell origin (>90% of malignant tumors) and most often presents at an advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulosa cell tumors, rather than adenocarcinomas. Induction of adenocarcinoma in 10-45% of rats following an ovarian implantation of 7,12-dimethylbenz[a]anthracene (DMBA) coated silk suture has been reported. Here, DMBA of 99% purity was melted at 124 degrees C to impregnate a 1 cm length of sterile suture for direct ovarian implantation in Wistar Furth rats at 7 weeks of age. DMBA-treated ovaries showed a nearly complete loss of primary follicles and degeneration of granulosa cells at 16 weeks, consistent with the known toxic response of the ovary to direct DMBA application. No tumors were present. Untreated right ovaries and sham dimethyl sulfoxide-treated ovaries were normal. Ovarian tumors in DMBA-treated rats were first noted at 26 weeks post implantation reaching a cumulative tumor incidence of 77% (23/30) at 52 weeks. Controls showed no evidence of tumor at 52 weeks (0/31). Tumor histology was distributed as well differentiated adenocarcinoma (1/23), poorly differentiated adenocarcinoma (8/23), thecal/granulosa cell tumor (8/23), undifferentiated sarcoma (5/23) and one undifferentiated carcinoma with no adeno character. Tumors occasionally seeded to peritoneal mesentery, spleen and abdominal wall. Adenocarcinomas appeared to originate from the ovarian surface epithelium, with focal papillary extension into cystic space. Epithelial derived tumor cells positively react with antibodies to cytokeratin (8/8), epithelial cell adhesion molecule (Ep-CAM 5/5) and prostaglandin synthetase-1 (COX-1 4/4). Vimentin positive epithelial cells when present in adenocarcinomas (4/7), showed perinuclear staining, quite distinct from the uniformly stained stromal cells in thecal/granulosa cell tumors (8/8). The thecal/granulosa cell tumors were Ep-CAM negative (0/5) and weakly COX-1 positive (4/4). Thus, the DMBA suture model in rats yields epithelial derived tumors histologically similar to humans and should prove suitable for the testing of preventive or therapeutic agents.     

Mechanism of ovarian carcinogenesis: effect of 7,12-dimethylbenz[a]anthracene administration on intrasplenic ovarian grafts in unilaterally ovariectomized C3HeB/Fe mice.

A single oral administration of 7,12-dimethylbenz[a]anthracene (DMBA) 2 weeks after intrasplenic grafting of ovarian tissue in unilaterally ovariectomized C3HeB/Fe mice resulted in a high tumor incidence (47%) in the grafted tissue, with only 1 tumor (3%) in the orthotopic ovary. No tumors were seen in the control group (unilaterally ovariectomized mice given intrasplenic grafts of ovarian tissue without subsequent DMBA administration), nor did tumors develop in response to DMBA treatment in mice with both ovaries in situ and no grafted tissue in the spleen. The results indicated that some local change caused by the grafting procedure rendered the tissues more sensitive to the action of DMBA and/or more responsive to gonadotropic stimulation.     

Effect of cycloferon on the evolution of cervical and vaginal cancer in mice

7,12-dimethylbenz(a)anthracene (DMBA) was given by tampon intravaginally to 198 mice CBA (9 groups), twice a week, for 2 months, to induce cervical and vaginal tumors. Cycloferon (CF)--an interferon inductor--was injected in study group animals subcutaneously and/or introduced into the vagina by smear, in 2-month courses. CF was given during DMBA treatment or after it. Controls were injected saline solution, sc, and/or received placebo smears, i.v. The experiment was run for 6 months. Tumor incidence in controls was 35-70%. Carcinogenesis tended to slow down when CF was given during DMBA treatment. Neoplasia was found in 38-57%. More marked anticarcinogenic effect was registered in animals receiving CF on termination of DMBA application: tumor frequency dropped to 29-41%, with malignant tumor number significantly reduced.     

Effects of high dietary fat on the growth and development of ovarian-independent carcinogen-induced mammary tumors in rats

This study examined the influence of high dietary fat intake on the development of ovarian-independent mammary tumors in both vehicle-treated controls and rats made deficient in estrogen and prolactin during tumor induction. The majority of 7,12-dimethylbenz(a) anthracene (DMBA)-induced mammary tumors in rats are dependent on estrogen and prolactin for growth, and suppression of prolactin and estrogen at the time of tumor initiation causes a reduction in tumor incidence and increase in tumor latency. However, the majority of mammary tumors which do develop in these animals exhibit ovarian-independent growth. Sprague-Dawley rats were given 7.5 mg DMBA p.o. at 57 days of age. Starting 1 day prior to and continuing for 7 days after DMBA administration, rats were given daily injection of vehicle or the combination of tamoxifen (20 micrograms/rat) plus bromocryptine (5 mg/kg). At the end of drug treatment, rats in each treatment group were equally divided and placed on normal fat (5% corn oil) or high fat (20% corn oil) diets for the duration of the experiment. Vehicle-treated rats were ovariectomized 27 wk and drug-treated rats 47 wk after DMBA administration to determine tumor ovarian dependency. Vehicle-treated rats fed high fat diets showed significant increases in mammary tumor incidence and number as compared to similarly treated rats fed a normal fat diet, with approximately 80% of the tumors in each group being ovarian dependent. Likewise, tamoxifen-bromocryptine-treated rats fed a high fat diet showed a significant enhancement in mammary tumor number, although not incidence, as compared to similarly treated rats fed a normal diet. Tumors in these drug-treated groups displayed essentially the same incidence of ovarian dependence (23%). Tamoxifen-bromocryptine-treated groups displayed a 2-fold increase in latency of tumor appearance as compared to vehicle-treated controls; however, this long latency was not reduced when these rats were fed a high fat diet. These results demonstrate that high dietary fat stimulates ovarian-dependent and -independent mammary tumorigenesis in rats but does not influence the hormonal responsiveness of these tumors.     

Effects of carcinogen and/or mutagen on normal and gonadotropin-primed ovaries of mice

The influence of pregnant mare serum gonadotropin (PMSG) on the induction of ovarian tumors by carcinogen (DMBA) and/or mutagens (EMS and BMS) has been studied in Swiss albino mice. Priming of the ovaries of 6-week-old mice with PMSG (50 lU/mouse) 24 h before intragastric intubation of DMBA (5 mg/mouse) resulted in a significant increase in ovarian tumors when harvested 6 months after the treatment. A similar experiment done on 8-week-old mice yielded confirmatory results. Mutagens (EMS and BMS) failed, at given dose levels (200 mg/kg and 300 mg/kg body weight), to induce tumors in normal as well as PMSG-primed ovaries. Nor could these mutagens enhance DMBA-induced tumor incidences in normal or PMSG-primed ovaries. Pretreatment of animals with PMSG-enhanced DMBA-induced oocyte depletion and also increased the DMBA-³H activity in the ovaries. The augmentation of DMBA-induced tumors in PMSG-primed ovaries could be due to increased uptake of DMBA and increased depletion of oocytes. It is also possible that PMSG-primed ovaries provided more proliferating granulosa cells (and macromolecules) for the interaction of DMBA (or its metabolites) and thereby increased the chances of cell transformation in the ovaries.