用环磷酰胺建立小鼠免疫抑制动物模型

目的比较用环磷酰胺(CTX)诱导正常小鼠免疫抑制的两种方法,选择合适的免疫抑制动物模型以评价保健食品的安全性。方法以环磷酰胺为受试物,设立正常对照组、CTX-1组和CTX-2组;正常对照组每日灌胃蒸馏水,CTX-1组每日灌胃60mg/kg环磷酰胺,CTX-2组于试验结束前一天腹腔注射200mg/kg环磷酰胺,试验周期为30天。观察不同剂量及不同方式给予环磷酰胺后对小鼠各项免疫指标的影响。结果CTX-1组小鼠体重、脾脏重量、外周血淋巴细胞计数、NK细胞活性、细胞毒性T细胞活性、HC50均低于对照组(P0.05),CTX-2组小鼠外周血T淋巴细胞(%)、Th细胞(%)、Ts细胞(%)及Th/Ts比值较对照组增高(P0.001,P0.001,P0.05,P0.05,P0.001),其它各项指标均较对照组降低(P0.05)。结论灌胃给予60mg/kg环磷酰胺30天与一次性腹腔注射200mg/kg环磷酰胺均可建立小鼠免疫低下模型,但前者更适用于建立评价保健食品安全性的免疫低下模型。     

银杏叶提取物对免疫抑制小鼠免疫功能的影响

目的探讨银杏叶提取物(Ginkgo biloba extract,EGB)对环磷酰胺(cyclophosphanmide,CTX)免疫抑制小鼠的免疫调节作用。方法健康昆明小鼠150只,随机分为对照组(Control)、CTX、EGB低、中、高剂量(EGB4、10、20 mg/kg bw)5组。实验前CTX和EGB各组腹腔注射CTX 100 mg/kg bw 3 d,之后EGB各组对应灌胃EGB 4、10、20 mg/kg bw,对照组和CTX组灌胃等容积生理盐水,1/d,连续15 d后测定免疫器官指数、廓清指数、血清溶血素、脾淋巴细胞增殖和细胞因子等免疫指标。结果与对照组比较,CTX组脾脏指数、胸腺指数、校正廓清指数、血清溶血素、脾淋巴细胞增殖能力和血清IL-6水平等均显著降低(P<0.01或P<0.05)。与CTX组比较,EGB-M、EGB-H剂量组脾脏指数显著提高(P<0.01,P<0.05),EGB-L组的胸腺指数无显著差异,EGB-M、EGB-H组胸腺指数显著增加(P<0.05,P<0.01),且呈剂量效应。EGB-H组的校正廓清指数和血清溶血素水平与CTX组相比均有差异显著性(P<0.05),且呈剂量效应。与CTX组比较,EGB-M、EGB-H组脾淋巴细胞的增殖能力和小鼠血清IL-6水平显著增加(P<0.01或P<0.05),且淋巴细胞增殖能力呈明显剂量效应,血清IFN-γ水平无显著差异。结论 EGB可以提高免疫抑制小鼠的非特异性免疫、体液免疫和细胞免疫功能。     

精氨酸双糖苷对环磷酰胺致免疫抑制小鼠免疫功能的影响

目的研究精氨酸双糖苷(arginyl-fructosyl-glucose,AFG)对环磷酰胺(CTX)诱导的免疫抑制小鼠免疫功能的影响。方法取BALB/C小鼠脾淋巴细胞,以不同浓度AFG(1,2,4,6,8,10μg/ml)刺激淋巴细胞的体外转化。另取ICR小鼠80只,随机分为8组:正常对照组(N)和免疫抑制模型组(M)给予生理盐水,免疫抑制给予AFG组:M+AFG-H,M+AFG-M和M+AFG-L,三组分别给予50,30,10 mg/kg bw AFG,正常给AFG组:N+AFG-H,N+AFG-M和N+AFG-L三组对应给予高中低50,30,10 mg/kg bw AFG。免疫抑制对照组及M+AFG-H,M+AFG-M,M+AFG-L在第1、2、3、9、16、23、30 d小鼠腹腔注射CTX 80mg/kg。测定AFG对BALB/C小鼠淋巴细胞体外转化的影响。30 d后处死ICR小鼠,测定胸腺指数和脾脏指数。AFG对脾淋巴细胞自然转化,T细胞转化,B细胞转化的影响,以及肿瘤坏死因子-α(TNF-α)及白细胞介素-2(IL-2)含量。结果高中低剂量AFG均能显著提高免疫抑制小鼠的脾脏指数和胸腺指数(P0.01,P0.05=。AFG对于体外脾淋巴细胞转化的促进作用随浓度的增大而增大,加药剂量为1~10μg/ml时,转化率呈浓度依赖性。AFG中剂量能显著促进免疫抑制小鼠脾细胞的自然转化(P0.05),而AFG低剂量能极显著促进脾淋巴细胞的自然转化(P0.01);高剂量AFG对于免疫抑制小鼠T淋巴细胞的转化具有显著性(P0.05);高中低剂量AFG均能显著促进免疫抑制小鼠B淋巴细胞的转化(P0.01,P0.05)。AFG高中低剂量均能显著提高免疫抑制小鼠血清中TNF-α(P0.01),其中高中剂量均能显著增加IL-2含量(P0.01,P0.05)。结论 AFG具有很强的免疫增强活性并能拮抗CTX的免疫抑制作用。     

环磷酰胺对小鼠免疫抑制的动物模型建立

[目的]建立肿瘤化疗免疫抑制动物模型，为建立保健食品减轻化疗毒副作用功能的评价方法提供科学依：活。[方法]给予C57BL／6J正常小鼠和荷瘤小鼠腹腔内注射不同剂量的环磷酰胺(CP)，隔日连续腹腔注射4—5次，观察：对小鼠免疫学指标及肝肾功能的影响。[结果]正常小鼠和荷瘤小鼠腹腔注射20、50、100me／kg体重的CP后，各剂量组均出现不同程度的免疫抑制和肝肾功能损伤。①正常小鼠20mg／kg体重以上剂量组，白细胞计数、抗体生成细胞以及巨噬细胞功能显著下降，谷草转氨酶(AST)升高；50mg／kg体重剂量组的脾脏指数下降；50mg／kg体重以上剂量组天然杀伤细胞(NK)细胞活性均出现显著下降，以及谷丙转氨酶、尿素的升高。②荷瘤小鼠20mg／kg体重以上剂量组白细胞计数、巨噬细胞功能显著下降，50mg／kg体重以上剂量组脾脏指数、NK细胞活性、抗体生成细胞功能均出现显著下降，以及谷草转氨酶、各丙转氨酶、尿素的升高。③正常小鼠注射60mg／kg体重的CP后，血清白细胞介素-2及肿瘤坏死因子均出现显著下降；荷瘤小鼠注射60mg／kg体重的CP后，血清白细胞介素．2出现显著下降。[结论]给予C47BL／6J正常小鼠和荷瘤小鼠腹腔注射20-50mg／kg体重的CP，隔日连续45次，即可建立免疫抑制动物模型。建议采用正常小鼠免疫抑制模型。     

黑加仑多糖对免疫功能调节作用的实验研究

目的:研究黑加仑多糖对免疫功能低下小鼠的免疫调节作用。方法:给小鼠腹腔注射环磷酰胺,建立小鼠免疫功能低下模型后,以0.4,0.8和1.6g/kg的黑加仑多糖灌胃,连续10d,另设模型对照组和正常对照组。观察免疫低下小鼠的脾、胸腺指数变化情况;用分光光度法测定小鼠巨噬细胞吞噬数、抗体分泌细胞生成数、血清溶血素和IL-2等免疫指标的含量。结果:黑加仑多糖高、中、低剂量组对免疫功能低下小鼠的脾、胸腺指数有增强作用,IL-2产生增加,增强血清溶血素的功能(P0.05),其中高、中剂量组对巨噬细胞吞噬功能有增强作用(P0.05)。黑加仑多糖高剂量组对免疫功能低下小鼠抗体分泌细胞功能有增强作用(P0.05)。结论:黑加仑多糖具有增强免疫功能的作用。     

IL-12单克隆抗体对克罗恩病模型小鼠Th1/Th2免疫平衡的调节作用

目的研究白细胞介素-12(IL-12)单克隆抗体对克罗恩病模型小鼠辅助性T细胞1/辅助性T细胞2(Th1/Th2)免疫平衡的调节作用。方法选择BALB/c健康小鼠30只,将30只小鼠分为正常对照组(10只)和实验小鼠(20只),实验组小鼠做克罗恩病模型,建模成功后将实验组小鼠分为克罗恩病组和IL-12单克隆抗体组各10只,IL-12单抗组小鼠腹腔注射IL-12单抗(25 mg/kg),正常对照组和克罗恩病组小鼠腹腔注射0.2 ml的生理盐水。处理4周后,对三组小鼠疾病活动程度、结肠重量、结肠长度进行评价,使用酶联免疫吸附试验法检测三组小鼠结肠组织中Th1型细胞因子干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、IL-1β、IL-8和Th2型细胞因子IL-4、IL-10及IL-12、IL-23表达水平。结果克罗恩病组小鼠疾病活动程度评分、结肠组织中Th1型细胞因子IFN-γ、TNF-α、IL-1β、IL-8、IL-12、IL-23分别为(4.12±0.23)分、(563.49±21.36)ng/ml、(120.69±6.69)ng/L、(43.73±3.58)ng/ml、(179.68±4.26)ng/ml、(148.69±6.58)ng/L、(762.58±26.58)pg/ml高于IL-12单克隆抗体组(1.62±0.17)分、(472.59±15.64)ng/ml、(106.25±3.27)ng/L、(37.62±2.16)ng/ml、(163.57±3.12)ng/ml、(98.67±5.12)ng/L、(412.68±16.98)pg/ml)和对照组,而结肠重量/长度为(42.36±3.16)mg/cm大于IL-12单克隆抗体组(33.59±2.07)mg/cm)和对照组小鼠;结肠组织中Th2型细胞因子IL-4、IL-10为(55.27±1.62)pg/ml、(90.27±3.68)pg/ml低于IL-12单克隆抗体组(61.27±2.21)pg/ml、(98.67±1.68)pg/ml)和对照组(P<0.05)。结论IL-12单克隆抗体通过改善Th1型细胞因子、Th2型细胞因子的异常表达,对Th1/Th2免疫平衡进行调节,进而抑制克罗恩病的炎症反应,起到治疗的效果。     

硫酸氨基葡萄糖对正常小鼠免疫功能的影响

目的了解硫酸氨基葡萄糖对正常小鼠免疫功能的影响。方法将ICR雌性小鼠按体重随机分成低、中、高(150、300、900mg/kg bw)3个剂量组和对照组。连续灌胃30天后,进行脾指数、胸腺指数、细胞免疫、体液免疫、NK细胞、单核-巨噬细胞及NK细胞活性的测定。结果高剂量组小鼠的胸腺指数显著高于对照组(P<0.05);中、高剂量组小鼠迟发型超敏反应(DTH)应激能力、血清溶血素水平及抗体生成能力明显高于对照组(P<0.05);高剂量组小鼠的NK细胞的活性显著高于对照组(P<0.05);硫酸氨基葡萄糖对小鼠脾淋巴细胞的增殖转化能力、腹腔巨噬细胞吞噬鸡红细胞的吞噬率、碳廓清吞噬指数均无影响。结论硫酸氨基葡萄糖从细胞免疫功能、体液免疫功能及NK细胞活性方面能增强正常小鼠的免疫功能。     

rhIL-18对辐照小鼠免疫功能的调节作用

目的研究重组人白细胞介素18(rhIL-18)对辐照小鼠免疫功能的调节作用,探讨rhIL-18在辐照防护中的应用价值。方法将32只小鼠随机分为正常对照组、单纯辐射照射组、rhIL-18+辐射照射组、辐射照射+rhIL-18组,辐照剂量为60Coγ射线4.0Gy,rhIL-18为0.6mg腹腔注射,处理后分别用淋巴细胞转化实验、NK细胞毒实验、T淋巴细胞亚群检测,测定小鼠脾细胞体外培养上清中白细胞介素-2(IL-2)、γ-干扰素(IFN-γ)、单核巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和血清中IgG的含量,观察rhIL-18对其免疫功能的调节作用。结果与单纯辐射照射组比较,rhIL-18能提高辐照后小鼠的T、B淋巴细胞转化能力(P0.05),使T、B淋巴细胞转化能力恢复或超过正常对照组水平,辐射照射后注射rhIL-18组的刺激指数达到了2.9〔刀豆蛋白A(ConA)组〕和6.1〔脂多糖(LPS)组〕;可促进辐照所致NK细胞活性抑制的恢复(P0.05),使NK细胞对肿瘤细胞杀伤率达到21.8%～35.6%;上调CD4T细胞数量,达到50个/ml(P0.05),提高辐照小鼠脾细胞分泌IFN-γ、GM-CSF和IL-2的能力(P0.05),但对IL-4分泌能力和IgG产生能力没有调节作用。结论rhIL-18具有促进辐照小鼠免疫功能恢复的作用。     

樟芝多糖对免疫抑制小鼠的免疫调节作用

目的探究樟芝多糖对于环磷酰胺构建的免疫抑制小鼠模型的免疫功能的调节作用。方法利用水提醇沉原理提取得到3种樟芝多糖,环磷酰胺构建免疫抑制小鼠模型。应用3种樟芝多糖进行干预,分别检测细胞免疫和体液免疫的相关指标,包括胸腺指数、脾脏指数、T淋巴细胞亚群、淋巴细胞增殖活性、自然杀伤(NK)细胞杀伤能力以及血清中白介素-2(IL-2)、白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、免疫球蛋白A(IgA)、IgG、IgM的表达。结果环磷酰胺构建的免疫抑制小鼠的免疫功能得到全面抑制,而3种樟芝多糖可以不同程度的提高免疫抑制小鼠的免疫功能,且相同剂量下,90%乙醇沉淀得到的多糖效果优于其他两种(P0.05)。结论樟芝多糖可以提高免疫抑制小鼠的免疫能力,且90%乙醇沉淀的多糖效果更优。     

环磷酰胺和氢化可的松建立免疫抑制模型方法比较

目的比较利用环磷酰胺(CP)和氢化可的松(HY)两种药物诱导建立小鼠免疫抑制模型的方法。方法设立CP-1组、CP-2组、CP-3组和HY组,相对应地设4个阴性对照组。CP-1组于第1、2、3、9、16和23天腹腔注射80mg/kg CP;CP-2组第1、3、5、7和9天腹腔注射50mg/kg CP;CP-3组d1、d2腹腔注射40mg/kg CP;HY组d1、d3、d5、d7和d9肌内注射40mg/kg HY。阴性对照-1、2、3组腹腔注射等剂量生理盐水,阴性对照-4组肌内注射等剂量生理盐水。分别于第29、11、7和10天测定各项免疫指标。结果CP组小鼠胸腺指数、抗体生成细胞数、半数溶血值(HC50)、白细胞计数与阴性对照组比较均降低(P<0.05)。HY组小鼠脾指数、胸腺指数、碳廓清吞噬指数、腹腔巨噬细胞吞噬荧光微球功能、NK细胞活性、迟发型变态反应、白细胞计数与阴性对照组比较均降低(P<0.05)。结论 CP和HY均可建立小鼠免疫抑制模型,各种指标对两种受试物的敏感性不同。     

应用细菌回复突变试验研究贻贝中麻痹性贝毒的致突变性

目的 了解贻贝中麻痹性贝类毒素的致突变性。方法 采用TA97、TA98、TAl00、TAl02测试菌株,在-S9和+S9条件下分别对0.0029～1.83 μg STX/皿剂量范围内的贻贝中麻痹性贝类毒素进行检测。结果 在2种不同的条件下,各剂量水平的4种测试菌株都能正常生长;所有剂量的回变菌落数与对照组相比均无1倍及以上的显著增加,且无剂量-反应关系。结论 在该试验条件下,贻贝中麻痹性贝毒未见致突变性作用。     

Effect of dietary n-3 and n-6 oils with and without food restriction on activity of antioxidant enzymes and lipid peroxidation in livers of cyclophosphamide treated autoimmune-prone NZB/W female mice

OBJECTIVE: Cyclophosphamide (CTX), an alkylating agent, is extensively used in the treatment of lupus nephritis, but its administration has been associated with free radical mediated oxidative stress. The present study was designed to investigate the effect of dietary corn oil (CO), fish oil (FO) and food restriction (FR) on the activities of hepatic antioxidant enzymes, fatty acid composition and lipid peroxidation following CTX administration in autoimmune-prone NZB/W female mice. METHODS: Autoimmune-prone NZB/W female mice were fed either ad libitum (AL) or food restricted (60% of AL intake), semipurified diets containing 5% CO or 5% FO supplemented with equal levels of antioxidants and injected with either phosphate buffered saline (PBS), or CTX (50 mg/kg body weight) every 10 days. Proteinuria was measured biweekly. The treatment was stopped at 10 months and diets were continued until the mice were killed at 12 months. Fatty acid composition, activity of antioxidant enzymes and lipid peroxidation were analyzed in liver homogenates, and anti-DNA antibodies were analyzed in the serum. RESULTS: Mice in the FO/AL dietary group exhibited significantly higher liver catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities compared to the CO/AL dietary group. CTX significantly decreased SOD and GSH-Px activity in the FO/AL group and CAT and GSH-Px in the CO/AL group. In AL fed mice given CTX, activities of CAT, GSH-Px and GST were significantly higher in mice fed FO diets than in mice fed CO diets. FR increased the activity of enzymes in both the CO and FO diet groups. In FR mice, CTX decreased CAT and GSH-Px activity in both the CO and FO dietary groups, but glutathione S-transferase (GST) only in the CO group. The decrease in SOD activity was not significant in either of the restricted groups. CTX significantly increased generation of thiobarbituric acid reactive substances (TBARS) in both AL groups. FR significantly decreased lipid peroxidation in both the CO and FO groups, with or without CTX. CTX decreased serum anti-DNA antibody levels in both the CO and FO dietary groups. FR also decreased antibody titer in both the CO and FO dietary groups, and it was decreased further with CTX treatment. FO fed animals had higher levels of n-3 fatty acids, whereas CO fed animals had high levels of n-6 fatty acids. CTX significantly increased 20:4 and decreased 18:1 in CO/AL fed animals, whereas it increased 18:1 and decreased 22:6 in FO/AL fed animals. CONCLUSIONS: Results obtained in the present study suggests that FO and, more significantly, FO combined with FR can have a beneficial effect in hepatic tissues subjected to CTX induced oxidative stress by regulating the activity of antioxidant enzymes. In addition, the study also indicates that n-3 and n-6 dietary lipids are susceptible to lipid peroxidation, particularly in the presence of a prooxidant like CTX, and that FR is beneficial in decreasing lipid peroxidation. The study also suggests that FO and CTX can have additive effects in preventing kidney disease in NZB/W mice.     

The use of respiratory enzymes as biomarkers of petroleum hydrocarbon exposure in Mytilus edulis planulatus

The effect of exposure to petroleum hydrocarbons via the water column and through contaminated sediment upon changes in respiratory enzymes in the common mussel (Mytilus edulis planulatus) was investigated. Mussels were exposed to three concentrations of the water-accommodated fraction (WAF) of Bass Strait crude oil, for 24, 48, and 96 h. In a second study mussels were exposed to three concentrations of crude oil-contaminated sediment for 2 weeks and 1, 2, 4 and 6 months. Activities of citrate synthase (CS) and lactate dehydrogenase (LDH) were measured in the gills. In mussels exposed to WAF, a significant decrease in CS activity was observed over time (P<0.05), whereas treatment did not cause a significant change in CS activity (P>0.05); neither treatment nor time had an effect on LDH activity. Exposure to contaminated sediment did not have a significant effect on CS activity, however, time had a significant effect on CS activity (P<0.05). Both time and treatment had an effect on LDH activity (P<0.05). Results demonstrated that changes in gill CS and LDH are not sensitive biomarkers of petroleum hydrocarbon exposure in M. edulis planulatus.     

E838提高肿瘤化疗药物疗效及抗免疫抑制作用的研究

目的 观察E838联合环磷酰胺(CTX)抗淋巴瘤(LM)及其对CTX的减毒作用。方法 建立LM荷瘤小鼠模型,实验分对照组、CTX、不同浓度E838组、不同浓度E838+CTX组,比较各组间的差别。结果 所有E838治疗组瘤重明显小于对照组,联合用药组各项实验指标均好于CTX组。结论 E838对LM有抑制作用,并对CTX有增效及提高机体免疫作用。     

Microcosm tributyltin bioaccumulation and multibiomarker assessment in the blue mussel Mytilus edulis

Blue mussels, Mytilus edulis, were exposed to two different concentrations of tributyltin (TBT) in seawater, 1,000 ng Sn/L (C1 experiment) and 10 ng Sn/L (C2 experiment), for 4 d, in order to evaluate the bioaccumulation of TBT by mussels Mytilus edulis in microcosms and to test the ability of a multimarkers analysis to determine the effects of TBT on the biochemical parameters in mussels. Tissue burdens of Mytilus edulis were 204 +/- 7 and 2,120 +/- 4 ng Sn/g TBT after the 4-d tests for the C2 and C1 experiments, respectively. Analyses of dissected organs and/or tissues demonstrated that TBT accumulated to the greatest extent in gills in the C1 experiment and in the digestive gland in the C2 experiment. Bioconcentration factors (BCFs) were 12,100 +/- 300 and 2,000 +/- 10 for mussels exposed in the C2 and C1 experiments, respectively. The four biomarkers used in this work were acetylcholinesterase (AChE), glutathione S-transferase (GST), catalase (CAT) activities, and thiobarbituric acid-reactive substances (TBARS) contents. No significant changes were observed in the measured enzyme activities or in TBARS concentration after the 4-d TBT exposure.     

贻贝多糖胶囊毒理学安全性研究

目的:对贻贝多糖胶囊的食用安全性进行毒理学评价。方法:采用急性毒性实验、遗传毒性实验(Ames试验、小鼠骨髓微核试验、小鼠精子畸形试验)和30 d喂养试验进行评价。结果:小鼠经口MTD均大于15.0 g/kg,Ames试验、小鼠骨髓微核试验、小鼠精子畸形试验三项遗传毒性试验结果均为阴性。30 d喂养试验未见大鼠的生长发育、血液学、生化、脏器比及组织病理学有异常变化。结论:贻贝多糖胶囊急性毒性分级属无毒级,无遗传毒性,最大无损害作用剂量大于1.6 g/kg,相当于人体推荐摄入量的120倍。在本实验剂量范围内,贻贝多糖胶囊属安全性保健食品。     

苦瓜多糖对链脲佐菌素诱导糖尿病小鼠的降血糖效果

目的:研究苦瓜水提多糖(watersolublepolysaccharidesofMomordicacharantiaL.MCW)和苦瓜碱提多糖(alkalinesolublepolysaccharidesofMomordicacharantiaL.MCB)对STZ诱导糖尿病小鼠的降血糖作用。方法:昆明种小鼠120只,随机抽取12只作空白对照,余下108只,禁食后于次日晨腹腔注射链脲佐菌素(STZ)200mg/kgbw。取血糖值在11.1mmol/L以上者随机分组,共4组:模型组、MCW组(300mg/kgbw)、MCB组(300mg/kgbw)和优降糖组(15mg/kgbw)。连续灌胃10d后,禁食,次日晨眼眶取血,测定血糖及血清胰岛素含量。解剖取胰腺,观察小鼠胰岛组织形态。结果:MCW和MCB都可以降低糖尿病小鼠空腹血糖,MCB组分的降血糖效果最佳,不但可以显著降低糖尿病小鼠空腹血糖值,而且可以提高糖尿病小鼠血清胰岛素水平。结论:苦瓜多糖能帮助恢复受损胰岛组织,促进胰岛素的分泌,从而降低血糖。     

Somatic and reproductive outcomes in mice treated with cyclophosphamide in pre-pubertal age

Disruption in the normal timing of female puberty, such as in pre-pubertal cancer treatments, can cause abnormal somatic development. We sought to evaluate the impact of cyclophosphamide (CTX) on the somatic, uterine, and ovarian, development of pre-pubertal mice. Pre-pubertal (day 18 of life) C57BL/6J female mice were randomized to receive placebo (group 1A and 1B), 200?mg/kg CTX (group 2A), or 120?mg/kg CTX (group 2B). Mice were euthanized on day 56 (A groups) or 95 (B groups) of life. Body weight and length, uterine and ovarian weight and right femur length and weight were measured, and ovarian insufficiency was assessed. Data were analyzed using ANOVA and t-test. Body weight and length did not differ among groups at time of euthanasia. The femur was shorter and weighed less in mice treated with CTX than in controls. Uterine weight was lower in group 2B than 1B (46.1?mg, 95% CI: 42.9-49.4, vs. 62.2?mg, 95% CI: 58.5-65.8, respectively; p?=?0.005) and was lower in mice that developed ovarian insufficiency than in mice that did not (p?<?0.05). Ovarian weight was lower in mice treated with CTX, regardless of whether they developed ovarian insufficiency. Even with no observable effect on adult body length and weight, CTX treatment in pre-pubertal mice appears to negatively affect femur, uterine, and ovarian development. However, uterine development seems to be dependent on the hormonal status created by CTX more than on its direct effect.     

Low dose radiation increased the therapeutic efficacy of cyclophosphamide on S(180) sarcoma bearing mice

We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in vivo. Kunming mice implanted with S(180) sarcoma cells were given 75 mGy whole body gamma-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by Western-blot. We discovered that tumor growth was significantly reduced in the group exposed to CTX add to LDR. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G(1) phase in the groups treated with CTX and CTX + LDR, but cell cycle was more significantly arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR or CTX chemotherapy. Concentration of bone marrow cells and proliferation index in CTX + LDR mice were higher than those in the untreated mice. LDR or CTX + LDR could induce greater cytochrome c levels and caspase-3 activity in tumors. These results suggest that low dose radiation can enhance the anti-tumor effect of the chemotherapy agent CTX markedly. Furthermore, LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance on adjuvant chemotherapy.