Mammary Tumour Development in BR6 Mice: Ovarian Influences and 5-Hydroxytryptamine

Pregnancy-dependent mammary tumours in BR6 mice first appeared during the third week of pregnancy. Regressed tumours reappeared chiefly during the second week. Alkaline Phosphatase activity in normal mammary tissue indicated a uniform increase in growth during pregnancy with no marked increase at any particular time. Pseudopregnancy was not sufficient to induce new tumours, though it had some stimulating effect on existing, regressed ones. 5-Hydroxy-tryptamine did not cause tumours in virgin mice, but seemed to influence tumour appearance in breeding females. Its possible mode of action is discussed.     

小鼠乳腺癌化疗放疗后顿抑癌细胞超微结构研究

目的：探讨小鼠乳腺癌化疗，放疗后存活顿抑癌细胞的超微结构特征。方法：TAⅡ乳腺癌小鼠36只，随机分为对照组，化疗组（环磷酰 ，5－氟脲嘧啶，氨甲喋呤）和放疗组（X射线），用电镜及电脑图像分析系统对治疗后残留的存活率细胞进行形态分析。结果：有效化疗和放疗后的癌组织绝大多数癌细胞已死亡，在坏死癌细胞中仍残留着形态完好的癌细胞。结构上分析这类细胞仍然存活，将其命名为顿抑癌细胞，并分为两类：Ⅰ型顿抑癌细胞和Ⅱ型顿抑癌细胞。顿抑癌细胞的平均体积明显小于对照组（P＜0．001），线粒体和粗面内质网的体密度也明显少于对照组（P＜0．001或P＜0．01），残留的顿抑癌细胞在对照组中也找到了同形的相应的副本对应细胞。结论：化疗，放疗后小鼠乳腺癌的顿抑癌细胞可能是癌局部复发的潜在危险因素。     

Contribution of Transient Blood Flow to Tumour Hypoxia in Mice

Tumours grown in mice typically exhibit regions of hypoxia believed to result from two different processes: chronic oxygen deprivation due to consumption/diffusion limitations, and periodic deprivation resulting from transient reductions in tumour blood flow. The relative contribution of each is, however, not generally known. We have addressed this issue in transplanted SCCVII squamous cell carcinomas in C3H mice, using a quantitative extension of the fluorescence 'mismatch' technique coupled with cell sorting from irradiated tumours. At least half of the vessels in these tumours exhibit transient perfusion changes. Additionally, a majority of the 15-20% of cells that are sufficiently hypoxic to be resistant to radiation in the SCCVII tumours appear to result from cyclic, not continuous (diffusion-limited) hypoxia. Since different strategies may be necessary to counteract cyclic hypoxia in tumours, the possibility of transient blood flow changes should not be ignored when planning cancer therapy for humans.     

新城鸡瘟病毒治疗肉瘤180小鼠的实验研究

肉瘤１８０（Ｓ_１８０）细胞注入到小鼠腹腔中制得荷瘤鼠模型，用新城鸡瘟病毒（ＮＤＶ）Ｂ１株治疗，观察１个月。青年鼠（７周龄）生存率达７６．７％，而老龄鼠（１年龄）和未经治疗的青年鼠均１００％死亡。病毒在Ｓ１８０腹水中基本不繁殖。进一步观察发现，经ＮＤＶ治疗的荷瘤鼠，７周龄鼠血清干扰素增高、ＮＫ细胞活性增强，而１年龄鼠中则未观察到此现象。７周龄鼠治疗后第４天可检测出抗病毒抗体，第８天时效价达１：１６００。用ＮＤＶ体外感染巨噬细胞也可诱生出较高浓度干扰素。结果提示，干扰素增高、ＮＫ细胞活性增强可能与抗肿瘤疗效有关，而抗病毒抗体与疗效间的关系，尚需进一步研究。     

Correlation of Tumour Response with Starting Tumour Size and Dose of Tamoxifen in an N-Methyl-N-Nitrosourea (NMU)-Induced Rat Mammary Cancer Model

Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and 500 μg/day) groups of six animals each, and another group (n=6) treated with TAM 100 μg/day at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.     

Prevention of Mammary Tumorigenesis in Acatalasemic Mice by Vitamin E Supplementation

Adult male and female acatalasemic (C3H/AnLCs^bCs^b), hypocatalasemic (C3H/AnLCs^cCs^c) and normal mice of C3H strain fed on regular laboratory chow for 15 months showed an increased incidence of spontaneous mammary tumor in the decreasing order of female acatalasemic, male acatalasemic, female hypocatalasemic and male hypocatalasemic mice. Normal mice did not develop mammary tumor. We conducted a prospective study with female acatalasemic mice, which showed the highest incidence of mammary tumor, to examine the preventive effect of vitamin E on mammary tumor. Female acatalasemic mice were fed on vitamin E-deficient (28 animals) and vitamin E-supplemented diet (25 animals) for 29 months. The incidence of mammary tumor in mice given the vitamin E-supplemented diet was 47%, while that in mice given vitamin E-deficient diet was 82% ( P <0.002). Mammary tumors were apparent after 9 months of vitamin E deprivation and after 14 months of vitamin E supplementation. Female normal mice did not develop mammary tumor during a comparable period of time. The mean catalase activity of mammary gland in acatalasemic mice was 18.8% of that in normal mice. The results indicate that vitamin E protects acatalasemic mice against the development of mammary tumor.     

大豆蛋白酶抑制物和皂甙抑瘤作用的实验研究

已有研究表明从大豆中提取的蛋白酶抑制物（ＰＩ）和皂甙有预防肿瘤的作用。本研究发现它们增加环磷酰胺（ＣＴＸ）对小鼠的抑瘤作用，又能减低对小鼠外周血细胞和骨髓有核细胞的毒性副作用，同是也发现它们对小鼠的免疫功能有促进作用。这些提取物可望作为人体肿瘤化疗的辅助用药。     

过氧基异丙苯对雄性小鼠的自由基毒性与遗传毒性的研究

背景与目的： 过氧基异丙苯是实验室常用的自由基激发剂,本实验旨在了解过氧基异丙苯(Cumene hydroperoxide,CHP)的自由基毒性和遗传毒性,为制造氧化损伤疾病相关动物模型提供参考剂量。 材料与方法： 36只健康昆明种成年雄性小鼠,体重(38.3±7.8) g , 随机分为4 组。灌胃染毒,染毒剂量分别为2 000、500、125和0 μg/kg。每天1 次,每周5 d,共计40 d。实验结束后处死小鼠,观察小鼠骨髓微核、精子畸变率,测定睾丸组织匀浆中丙二醛(Malondialdehyde,MDA)、 总超氧化物歧化酶(Total superoxide dismutase,T-SOD)、还原型谷胱甘肽(Glutathion,GSH)的水平。 结果： CHP染毒各组小鼠体重有程度不同的减轻,随染毒剂量的增加,睾丸组织匀浆中MDA含量逐渐增加,T-SOD活力、 GSH含量逐渐降低,其中2 000 μg/kg体重染毒组睾丸组织匀浆中MDA含量与对照组比较差异有统计学意义(P<0.01),500 μg/kg染毒组GSH含量、SOD活力与对照组比较差异有统计学意义(P<0.05);骨髓嗜多染红细胞微核及精子畸变率增高,2 000 μg/kg染毒组与对照组比较差异有统计学意义(P<0.01)。 结论： CHP对昆明种小鼠具有很强的自由基毒性和遗传毒性,CHP的自由基毒性引发的氧化损伤可能是其遗传毒性的重要机制。     

人内皮抑素基因腺病毒表达载体的构建及其在乳腺癌细胞中的表达活性

引言近年来,阻止肿瘤血管生成,控制肿瘤的生长和转移,成为肿瘤治疗的一项新策略[1,2],其中采用转染血管生成抑制剂拮抗血管的生成,以内皮抑素最为理想[3]。本文通过构建人内皮抑素基因的腺病毒表达载体,研究内皮抑素在乳腺癌细胞中的表达,为进一步研究乳腺癌的抗血管基因治疗做好准备。1材料与方法1.1材料携带人内皮抑素基因(humanendostatin,hE)的质粒pBlast hEndostatin购于美国InvitroGen公司;腺病毒载体pCA13、pBGHE3及293细胞株购于MicrobixBiosystems公司;人乳腺癌细胞株MBD231和MCF7、人脐静脉内皮细胞株ECV304购于美国ATCC细胞库;LipofectAMINE2000转染试剂盒购自GibcoBRL公司;各种限制性内切酶和DNA连接酶购自NEB公司;QIAprepspin miniprepkit、QIAampDNABloodMiniKit购自QIAGEN公司;M PERMammalianProteinEx tractionReagent购自PIERCE公司;Western显色液LumiGLOchemiluminescentreag...     

Production and Effect of Infectious Dane Particles in Transgenic Mice

We have demonstrated by immunoelectron microscopy that 42-nm particles with double-shelled structures characteristic of Dane particles are present in the serum of transgenic mice, 1.2HB-BS 10, carrying partly duplicated hepatitis B virus (HBV) genome. Furthermore, these particles were shown to infect primary human fetal hepatocytes as demonstrated by the elevation of MBV surface antigen (HBsAg) in the culture medium. HBV DNA is known to be expressed in a liver- and kidney-specific manner in the adult mouse, so we examined the developmental expression of viral antigens. In the liver, viral antigens (HBsAg and HBV e antigen) began to be expressed before birth and the level of expression showed a sharp rise after birth. On the other hand, in the kidney, viral antigens began to be expressed after birth. Serum levels of viral antigens were roughly proportional to the levels of expression in the liver, suggesting that the liver is the main source for viral antigens in the serum. None of these transgenic mice produced anti-HBs or anti-HBV core response or showed biochemical or pathological change up to at least 24 months of age. All these results suggest that infectious viral particles can be produced in transgenic mice, and that expression and replication of HBV DNA are not toxic in vivo.