1,2:5,6一二去水卫矛醇抗肿瘤作用及毒性

1,2:5,6—二去水卫矛醇(DAG)对体外培养的S_(180)细胞的IC_(50)为0.1—1.0ug/ml。对大鼠W_(256),小鼠实体型S_(180)、S_(37)、U_(14)、Heps及小鼠腹水型S_(180)、FepA、EAC、L_(1210)等均有效,其中对W_(25)~6(1.2mg/kg/d×7,ip)及L_(1210)(8.0mg/kg×     

甲基苯丙氨酸氮芥(AT-1420)抗瘤作用的研究

AT-1420即甲基苯丙氨酸氮芥。实验表明对大鼠W-255有显著的抗瘤活性,用0.155～1mg/kg/d×7,有 81～100％抑瘤率,用0.25～1mg/kg/d×7,有50～100％肿瘤消散率,疗效与消瘤芥相似。 对小鼠S-180,肝癌、网细胞肉瘤(L_2)均有明显的抗瘤作用,用0.6～0.8mg/kg/d×7～8腹腔给药,抑瘤率分别为48～52％,28％、41～50％,对艾氏腹水癌(EAC)生命延长率为177％。作为比较,消瘤芥用量为2.5～3.5mg/kg/d,对S-37抑制率为64％。AT-1420对EAC和W-256疗效较好,但对S-37无效,其他肿瘤和消瘤芥的疗效相似。另口服和注射给药均有效。 AT-1420对~3H-TdR参入EAC细胞中有明显的抑制作用,抑制率为70％(±8.1)。 测得大鼠腹腔注射一次的LD50为5.4mg/kg,7次给药的LD50为1.25mg/kg/次。测得小鼠腹腔注射一次的LD50为8mg/kg,而7次给药的LD50为1.13mg/kg/次。 上述表明AT-1420有明显的抗动物肿瘤作用,抗瘤谱广,口服和注射给药有效。疗效与消瘤介相似,且用量较小,故AT-1420值得进一步研究,考虑提供临床试用。     

喜树碱(CPT)与10—羟基喜树碱(HCPT)的抗肿瘤活性与毒性比较

给小鼠一次腹腔注射(ip),CPT的LD_(50)为65.7±11.3mg/kg,HCPT为149.6±29.7mg/kg。“等毒性”剂量的HCPT对腹水型肝癌(HepA)、艾氏腹水癌(EAC)及肉瘤180(S_(180))小鼠的抗癌作用强于CPT。二药均能抑制HepA细胞DNA、RNA合成及膜的核苷转运。CPT及HCPT对HepA小鼠的治疗比分别为2.5和25,HePT对小鼠的骨髓毒性明显低于CPT。     

顺铂对小鼠淋巴细胞性白血病及小鼠淋巴细胞肉瘤疗效观察

本文报告顺铂(cisplatin)不但对小鼠SRS淋巴肉瘤有显著疗效,而且对小鼠L_(783)淋巴细胞性白血病及小鼠L_(6565)淋巴细胞性白血病亦有显著疗效。一次用药即可使小鼠SRS腹水型淋巴肉瘸0％“治愈”;剂量以8mg/kg为宜;用药时间以小剂量间断给药即第1、5、9天Q6H用药疗效更佳。本药对中、晚期肿瘤亦有效。本实验所用药物为大连医学院乔谢民教授所领导的顺铂研究室所合成,所用之瘤株为上海第一医学院病理生理教研室程立副教     

吉西他滨缓释微球急性毒性实验研究

目的 了解乳酸-乙醇酸共聚物(PLGA)-吉西他滨缓释微球和吉西他滨小鼠皮下给药的急性毒性.方法 采用上下增减剂量法(UDP)分别测定PLGA-吉西他滨缓释微球和吉西他滨小鼠皮下给药对动物的半数致死量(LD50).结果 PLGA-吉西他滨缓释微球皮下给药的小鼠LD50为256.30 mg/kg,吉西他滨小鼠皮下给药时为8.91 mg/kg,相差达28.8倍.结论 PLGA-吉西他滨缓释微球能够显著降低化疗药物对动物的急性毒性.     

三聚氰胺与三聚氰酸对小鼠的联合急性毒性

目的： 研究不同比例的三聚氰胺 (melamine,M)与三聚氰酸 (cyanuric acid,C )联合给药对小鼠的联合急性毒性。方法：选择SPF级昆明种小鼠240只,随机分为20组,每组12只,雌雄各半。采用寇氏法研究三聚氰胺与三聚氰酸 (M+C)对小鼠的联合急性毒性,M+C按1∶1、2∶1、1∶2三种比例混合经口一次性灌胃给药。每种比例设立6个剂量组即109、173、274、435、689和1 092 mg/kg,灌胃容量为0.02mL/g。并设溶剂对照组(给予等体积的玉米油),另设空白组。动物给药后记录生长情况、死亡情况、死亡动物体质量与肾脏质量,连续观察14 d,计算半数致死剂量 (median lethal dose,LD50)。第15 天将存活动物全部脱臼处死,解剖观察,记录动物体质量与肾脏质量。结果：M+C (1∶1)组,雄鼠LD50为274 mg/kg、雌鼠LD50为401 mg/kg;M+C (2∶1)组,雄鼠LD50值为401 mg/kg、雌鼠LD50值为546 mg/kg;M+C (1∶2)组,雄鼠LD50值为344 mg/kg、雌鼠LD50值为589 mg/kg。M+C 3种比例混合物经口灌胃,剂量为1 092 mg/kg时,动物均死亡;剂量低于173 mg/kg时,各组动物均无死亡。M+C各给药试验组,小鼠肾脏均发生病变,肾脏不同程度膨胀,表面可见斑点,肾脏脏器系数值大于两个对照组 (P<0.05)。结论：三聚氰胺与三聚氰酸混合物在1∶1比例下,经口毒性较大,对雄鼠的毒性大于雌鼠,可引起肾毒性。与单独三聚氰胺或三聚氰酸毒性相比,M+C联合毒性大。     

紫杉醇脂质体的体内外抗肿瘤作用研究

[目的]研究注射用紫杉醇脂质体的体外细胞毒作用和体内抗瘤作用及药物毒性。[方法]用MTT法检测紫杉醇脂质体对人肺腺癌细胞株SPC-A1的体外杀伤作用;建立小鼠实体型S180肿瘤模型,共50只,随机分为5组:5%葡萄糖溶液组(空白对照组)、紫杉醇注射液10mg/kg组和15mg/kg组,紫杉醇脂质体10mg/kg组和15mg/kg组,观察各组抑瘤作用和小鼠一般状态的变化,并检测肝功能和骨髓像改变。[结果]紫杉醇脂质体对体外培养的人肺腺癌细胞株SPC-A1在浓度为2.5ng/ml、5.0ng/ml和10.0ng/ml时,其抑制率分别为39.1%、51.9%和55.8%。体内给予紫杉醇脂质体10mg/(kg·d),15mg/(kg·d)3d,对小鼠S180实体型的抑瘤率分别为31.12%和45.29%,与同样剂量紫杉醇注射液组比较无显著性差异;给药后动物行为和小鼠体重变化率较紫杉醇注射液组接近对照组;骨髓抑制程度亦低于同剂量紫杉醇注射液组。[结论]相同给药剂量下,紫杉醇脂质体的体内外抗肿瘤活性与紫杉醇注射液相接近,但药物毒副反应明显降低。     

血卟啉铂络合物的抗癌实验研究

有人认为血卟啉铂络合物有一定的抗癌活性。据我们的实验研究观察:血卟啉后络合物对L_(1210)、HeLa及KB三种体外培养的肿瘤细胞无明显的直接杀伤作用;对S_(180)、ECA及L_(7712)三种腹水型小鼠移植性肿瘤亦无明显的抗癌效果。     

高三尖杉酯碱的抗癌疗效及药代动力学研究

目的：研究高三尖杉酯碱（HHRT）口服的抗癌疗效及其药代动力学。方法：用肿瘤生长抑制率和荷瘤动物生命延长率来评价HHRT口服的抗癌疗效。用反相高效液相色谱法（HPLC）法检测HHRT口服的药代动力学。结果：口服HHRT在剂量为0．5mg/kg和1．0mg/kg时,对小鼠肉瘤S180及小鼠EC实体癌均有明显疗效,抑制率为38．9％－50．5％;对小鼠腹水型肝癌（HepA)的生命延长率为87．5％;在研究不同给药方案对口服HHRT疗效的影响时发现,间隔给药组疗效与每天连续给药组相近,一次给药组没有明显的疗效;大鼠口服HHRT后,在血液中未检测到原药的存在。结论：口服HHRT具有明显的抗肿瘤作用,发挥此作用的并非原药本身。     

1,2-二甲基-3-羟基-4-吡啶酮遗传毒性的研究

背景与目的:研究1,2-二甲基-3-羟基-4-吡啶酮(DHPO)的急性毒性及不同剂量、不同时间的遗传毒性.材料与方法:采用昆明种小鼠,先进行LD50试验,然后对高(1/2 LD50)、中(1/4 LD50)、低(1/8 LD50)DHPO剂量组进行外周血和骨髓微核率的观察.结果:DHPO的小鼠经口LD50为562.34 mg/kg.外周血和骨髓微核试验显示,1/8 LD50(70 mg/kg)组、1/4 LD50(140 mg/kg)组微核率与阴性对照组相比差异均无统计学意义(P＞0.05);1/2 LD50(280 mg/kg)组微核率高于阴性对照组、1/8 LD50(140 mg/kg)组和1/4 LD50组(P均＜0.05).结论:DHPO属于低毒药物,具有小鼠体内染色体畸变的遗传毒性.     

美洲大蠊提取物CⅡ-3对肝癌H22荷瘤小鼠作用研究

目的 美洲大蠊提取物CⅡ-3在体内外有抑制肿瘤生长和改善免疫功能的作用.本研究在前期研究的基础上观察CⅡ-3单药对比联合环磷酰胺(cycolophosphamide,CTX)对小鼠肝癌H22移植性实体瘤的治疗效果,探讨C Ⅱ-3在肿瘤治疗中的作用.方法 建立Balb/c小鼠H22腋下实体瘤模型,并将80只小鼠随机分为对照组、CTX组(20 mg/kg)、CTX +CⅡ-3联合给药组(CTX 20 mg/kg,CⅡ-3 50、100和200 mg/kg)、CⅡ-3给药组(50、100和200 mg/kg).连续给药12 d后,测定其抑瘤率脏器指数,外周血细胞数量,T、B淋巴细胞转化功能及NK细胞杀伤活性.结果 对照组的瘤块质量为(1.21±0.28) g,CTX组为(0.73±0.27) g,CTX联合C Ⅱ-3低、中、高剂量给药后的瘤块质量为(0.40±0.21)、(0.43±0.11)和(0.41±0.19) g,C Ⅱ-3低、中、高剂量组的瘤块质量分别为(0.93±0.39)、(0.94±0.31)和(0.96±0.16) g,与对照组和CTX组相比,联合给药组肿瘤生长速度明显减慢,差异有统计学意义,F=8.916,P<0.05.CTX组白细胞的数量为(1.56±0.64)×109 L-1,CTX联合C Ⅱ-3低剂量组为(4.47±0.91)×109 L-1,显著改善外周血象,F=2.476,P<0.05.对照组小鼠肝脏指数为(6.101±0.412) mg/10 g,CTX组为(5.112±0.463) mg/10 g,中剂量C Ⅱ-3联合CTX给药后肝脏指数可高达(5.882±0.548) mg/10 g,减轻了CTX对肝脏的损伤,F=4.225,P<0.01.对照组小鼠脾脏指数为(0.659±0.148) mg/10 g,CTX组的脾脏受到严重损伤,其指数为(0.314±0.092) mg/10g,联合给药后可以显著地减轻CTX对脾脏的损伤,其指数为(0.569±0.033) mg/10 g,F=5.667,P<0.05;对照组小鼠的胸腺指数为(0.060±0.018) mg/10 g,给予CTX后小鼠的脏器受到严重的损伤,胸腺指数为(0.024±0.004) mg/10 g,C Ⅱ-3联合CTX给药后胸腺指数为(0.056±0.014) mg/10 g,减轻了CTX对胸腺的损伤,对胸腺有一定的保护作用,F=4.729,P<0.05.荷瘤小鼠在给予CTX治疗后,T、B淋巴细胞的转化功能及NK细胞杀伤力显著地降低(P<0.05,P<0.01),C Ⅱ-3联合CTX可提高T、B淋巴细胞的转化功能及NK细胞杀伤力(P<0.05,P<0.01),从而增强机体的免疫功能.结论 C Ⅱ-3联合CTX治疗H22荷瘤小鼠可提高抑瘤率,具有提高CTX治疗效果的作用,其增效作用是通过提高T、B淋巴细胞的转化功能及NK细胞杀伤力实现的.除此之外C Ⅱ-3还具有减毒作用,其减毒作用是通过改善白细胞、红细胞和血小板的数量,提高脏器指数实现的.     

Toxicology studies of sodium bromate (CAS No. 7789-38-0) in genetically modified (FVB Tg.AC Hemizygous) mice (dermal and drinking water studies) and carcinogenicity studies of sodium bromate in genetically modified [B6.129-Trp53tm1Brd (N5) haploinsufficient] mice (drinking water studies)

Bromate is a drinking water disinfection by-product formed during the ozonation of source water containing bromide. Sodium bromate is also used as an analytical reagent, in the oxidation of sulfur and vat dyes, and for cleaning boilers. As a mixture with sodium bromide, it is used for dissolving gold from its ores. The cosmetic industry uses sodium bromate and potassium bromate as neutralizers or oxidizers in hair wave preparations. Sodium bromate was nominated for toxicity and carcinogenicity studies in transgenic mouse models by the United States Environmental Protection Agency and the National Institute of Environmental Health Sciences. Male and female Tg.AC hemizygous mice received sodium bromate by dermal application for 26 or 39 weeks and by exposure in drinking water for 27 or 43 weeks. Male and female p53 haploinsufficient mice were exposed to sodium bromate (at least 99% pure) in drinking water for 27 or 43 weeks. Genetic toxicology studies were conducted in mouse peripheral blood erythrocytes. 26- and 39-WEEK DERMAL STUDIES IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice received dermal applications of 0, 64, 128, or 256 mg sodium bromate/kg body weight in ethanol/water, 5 days per week for 26 weeks. Additional groups of 10 male and 10 female Tg.AC hemizygous mice were dermally administered the same doses for 39 weeks. Survival of dosed groups was similar to that of vehicle control groups at 26 and 39 weeks. Mean body weights of 256 mg/kg males were less than those of the vehicle control group in both studies. Mean body weights of all dosed groups of females were less than those of the vehicle controls at 39 weeks. Minimal decreases in hematocrit and hemoglobin concentration values occurred in 128 mg/kg females and 256 mg/kg males and females at 26 weeks. A minimal decrease in erythrocyte count also occurred in 256 mg/kg males. These decreases in erythron were accompanied by a minimal decrease in mean cell hemoglobin and mean cell hemoglobin concentration values, primarily in the females. Reticulocyte counts were significantly increased in 128 mg/kg females and 256 mg/kg males and females. There were no increased incidences of neoplasms in male or female Tg.AC hemizygous mice exposed to sodium bromate dermally. Relative kidney weights were significantly increased in 256 mg/kg males at 26 weeks and in all dosed groups of males at 39 weeks. Absolute testis weights in 256 mg/kg males and absolute kidney weights in 256 mg/kg females were decreased at 39 weeks. Nephropathy occurred in 14 of 15 males receiving 128 and 256 mg/kg at 26 weeks and in all 256 mg/kg females in both studies. In the thyroid gland, the incidences of follicular cell hypertrophy in all dosed groups of males and females, follicular secretory depletion in 128 and 256 mg/kg females, and lymphocytic cellular infiltrate in 256 mg/kg females were significantly increased in both studies. Splenic hematopoietic cell proliferation occurred with a significantly increased incidence in 128 and 256 mg/kg females at 26 weeks. The incidence of germinal epithelium degeneration in the testis was significantly increased in 256 mg/kg males at 39 weeks. 27- AND 43-WEEK DRINKING WATER STUDIES IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 27 weeks (equivalent to average daily doses of approximately 13, 63, and 129 mg/kg to male mice and 15, 72, and 148 mg/kg to female mice). Additional groups of 10 male and 10 female Tg.AC hemizygous mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 43 weeks (equivalent to average daily doses of approximately 11, 52, and 131 mg/kg to male mice and 15, 65, and 152 mg/kg to female mice). Survival of exposed groups was similar to that of control groups at 27 weeks. Survival was decreased in 400 mg/L females and 800 mg/L males and females at 43 weeks. Mean body weights of 400 mg/L males and 800 mg/L males and females were less than those of the control groups in both studies. Water consumption by exposed mice was generally similar to that by control groups throughout both studies. Minimal decreases in hematocrit, hemoglobin concentration, and erythrocyte count values occurred primarily in 400 and 800 mg/kg females at 27 weeks. There were also decreases in mean cell hemoglobin and mean cell hemoglobin concentration values, but these occurred primarily in treated males. Reticulocyte counts were increased in 400 mg/kg males and 800 mg/kg males and females. There were no increased incidences of neoplasms in male or female Tg.AC hemizygous mice exposed to sodium bromate in the drinking water. Absolute kidney weights were significantly decreased in 800 mg/L females and relative kidney weights were increased in 400 and 800 mg/L males at 27 weeks. Absolute testis weights were significantly decreased in 800 mg/L males at 43 weeks. Thyroid gland follicular cell hypertrophy and follicular secretory depletion occurred in most 400 and 800 mg/L males and females at 27 weeks and in most exposed females at 43 weeks, and the incidences of thyroid gland follicular cell hypertrophy were significantly increased in all exposed groups of males at 43 weeks. The incidences of thyroid gland lymphocytic cellular infiltrates were significantly increased in 400 and 800 mg/L females in both studies and in 800 mg/L males at 43 weeks. The incidences of nephropathy were significantly increased in all exposed groups of males and in 400 and 800 mg/L females at 27 weeks. Renal tubule degeneration occurred with significantly increased incidences in 800 mg/L males and females in both studies. The incidences of renal tubule hypertrophy were significantly increased in 400 and 800 mg/L females at 27 weeks and in 800 mg/L males and females at 43 weeks. Pituitary gland pars distalis hypertrophy occurred with a significantly increased incidence in 800 mg/L females in both studies. The incidence of hyperkeratosis of the forestomach epithelium was significantly increased in 800 mg/L females at 43 weeks. The incidences of tubular degeneration of the epididymis and germinal epithelium degeneration of the testis were significantly increased in 800 mg/L males at 43 weeks. 27- AND 43-WEEK DRINKING WATER STUDIES IN p53 HAPLOINSURFFICIENT MICE: Groups of 15 male and 15 female p53 haploinsufficient mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 27 weeks (equivalent to average daily doses of approximately 8, 39, and 74 mg/kg to males and 13, 72, and 136 mg/kg to females). Additional groups of 10 male and 10 female p53 haploinsufficient mice were exposed to drinking water containing 0, 80, 400, or 800 mg/L sodium bromate for 43 weeks (equivalent to average daily doses of approximately 7, 37, and 65 mg/kg to males and 11, 58, and 107 mg/kg to females). In both studies, survival of exposed groups was similar to that of control groups. Mean body weights of 400 and 800 mg/L females were less than those of the control groups during most of the studies. Water consumption by exposed mice was generally similar to that by control groups in both studies. No neoplasms or nonneoplastic lesions in male or female p53 haploinsufficient mice were attributed to exposure to sodium bromate in either study. GENETIC TOXICOLOGY: Sodium bromate exposure resulted in significantly increased frequencies of micronucleated erythrocytes in male and female Tg.AC hemizygous and p53 haploinsufficient mice administered the chemical in drinking water for 27 weeks or by dermal application for 26 weeks. Tg.AC hemizygous mice were treated by both routes; p53 haploinsufficient mice were exposed only through drinking water. In all three micronucleus tests, a clear dose response was observed in male and female mice. Significant increases in the percentage of polychromatic erythrocytes among total erythrocytes were observed in male and female Tg.AC hemizygous mice exposed via drinking water and in male Tg.AC hemizygous mice dosed dermally with sodium bromate. The percentage of polychromatic erythrocytes was not significantly altered in male or female p53 mice. CONCLUSIONS: Under the conditions of these drinking water studies, there was no evidence of carcinogenic activity of sodium bromate in male or female p53 haploinsufficient mice exposed to 80, 400, or 800 mg/L for 27 or 43 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed dermally to 64, 128, or 256 mg sodium bromate/kg body weight for 26 or 39 weeks. No treatment-related neoplasms were seen in male or female Tg.AC hemizygous mice exposed by drinking water to 80, 400, or 800 mg sodium bromate/L for 27 or 43 weeks. In drinking water and dermal studies in Tg.AC hemizygous mice there were increased incidences of nonneoplastic lesions in the thyroid gland and kidney.     

YH-16对宫颈癌Hela细胞及其裸鼠皮下移植瘤作用研究

目的：初步探讨YH-16（重组内皮抑素）对宫颈癌Hela细胞及其荷瘤生长抑制作用及作用机制。方法：用MTY法检测YH-16对Hela细胞生长抑制作用；用透射电镜观察YH-16处理Hela细胞后的凋亡情况、流式细胞仪检测细胞凋亡率及细胞周期；将Hela细胞移植至裸鼠皮下成瘤，观察不同浓度YH-16（0mg／kg、0．4mg／kg、0．75mg／kg和1．5mg／kg）对荷瘤鼠皮下移植瘤生长的影响；TUNEL法观察肿瘤细胞的凋亡；免疫组化方法检测裸鼠移植瘤组织中肿瘤微血管密度（MVD）。结果：YH-16具有体外抑制Hela细胞增殖的作用（P〈0．01）；能诱导Hela细胞凋亡；YH-16能有效抑制裸鼠皮下移植瘤的生长（P〈0.05）；YH-1615mg／kg组的肿瘤MVD计数较对照组和其它治疗组明显降低（P〈0．05）。结论：YH-16具有抑制宫颈癌Hela细胞及其皮下移植瘤生长的作用。     

Immunosuppressive effects of sulfato-trans-(-)-1,2-diaminocyclohexaneplatinum(II).

Sulfato-trans-(-)-1,2-diaminocyclohexane platinum(II) is a new antitumor agent. Its effect on immune responses was investigated. This agent inhibited lymphocyte transformation in response to phytohemagglutinin, pokeweed mitogen, and concanavalin A. It inhibited antibody plaque-forming spleen cells in AKR/J mice at doses ranging from 2.5 to 7.5 mg/kg i.p. It also prolonged the survival of skin grafts against major histocompatibility barriers in C57BL/6J mice transplanted with tail skin from CBA/J mice. The effective dose ranged from 2.5 to 5 mg/kg. This compound inhibited graft-versus-host reaction in three-week-old AKR/J X DBA/2JF1 mice receiving spleen cells from AKR/J mice i.p. Significant inhibition of graft-versus-host reaction was seen with doses ranging from 1 to 7.5 mg/kg i.p. These results suggest that this drug is immunosuppressive.     

Enhancement of antitumor activity of 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine and Baker's antifol (triazinate) with carboxypeptidase G1.

Carboxypeptidase G1 (CPDG1), an enzyme that degrades folates but not the nonclassical folate antagonists triazinate (TZT, Baker's antifol) and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP), enhanced the antineoplastic activity of these antifolates. In 6-day cell culture experiments with Walker 256 carcinosarcoma, CPDG1 at levels up to 0.54 unit/ml showed very little inhibitory effect on growth. In the presence of 10(-7) M DDMP, the grown of Walker 256 cells was similar to that of controls, but in combination with CPDG1 (0.1 unit/ml) 80% growth inhibition was observed. TZT at a concentration of 10(-8) M did not affect the growth of Walker 256 cells. The combination of 10(-8) M TZT with CPDG1 (0.1 unit/ml), however, strongly inhibited cell growth. In experiments with rats bearing Walker 256 carcinosarcoma, the administration of CPDG1 (800 units/kg/day) from Day 1 to Day 6 resulted in no significant increase in life span. Administration of TZT in doses up to 0.05 mg/kg on Day 1 or that of DDMP up to 15 mg/kg on Days 1, 3, and 5 had no antitumor effects as measured by survival of the animals. However, CPDG1 (800 units/kg/day) from Day 1 to Day 6 in combination with TZT (0.05 mg/kg on Day 1) or DDMP (15 mg/kg on Days 1, 3, and 5) resulted in increases of 50 and 30%, respectively, in the survival of the tumor-bearing animals. These results demonstrate that CPDG1 enhances the antitumor effects of TZT or DDMP.     

NM-3对裸鼠移植胃癌组织VEGF—C、VEGF—D和VEGF—R-3表达的影响

目的：探讨NM-3对裸鼠移植人胃癌组织微淋巴管生成的影响及可能机制。方法：28只未分化人胃腺癌SGC-7901移植BALB／C裸鼠随机分为4组，每组7只，分别腹腔内注射生理盐水、NM-3、卡铂及NM-3加卡铂，每周2次，剂量为NM-310mg／kg，卡铂5mg／kg。于第8周末处死裸鼠，取下肿瘤组织，定量免疫组化染色检测移植瘤组织VEGF—C、VEGF—D和VEGF—R-3表达。结果：各组VEGF—C免疫组化染色阳性面积（μm^2）为：卡铂组（1647．83±501．70）、NM-3组（2106．01±437．11）及联合给药组（1825．61±277．24），均较生理盐水对照组（2962．84±519．77）显著下降（P〈0．05），各治疗组之间无显著差别。VEGF—D值：NM-3组（1032．25±460．44）及联合给药组（1009．08±370．13），较生理盐水组（1882．15±359．38）及卡铂组（1854．00±322．07）均显著下降（P〈0．05），卡铂组较生理盐水组下降，但是差别无显著意义。VEGF—R-3值：NM-3组（1222．05±470．80）及联合给药组（1103．34±265．94）较生理盐水组（2123．05±117．99）下降，并有显著意义（P〈0．05），而卡铂组（1668．30±256．34）与生理盐水组比较差异无显著性；各治疗组之间无显著差别。结论：NM-3能够抑制胃癌微淋巴管生成，并能增强卡铂的抗肿瘤作用。     

Use of the Comet Assay to Detect Hypoxic Cells in Murine Tumours and Normal Tissues Exposed to Bioreductive Drugs

The alkaline comet assay was applied to individual cells from mice exposed to two bioreductive drugs, tirapazamine and RSU 1069, with the goal of comparing DNA damage to tumours and normal tissues. More DNA single-strand breaks (SSBs) and a greater heterogeneity in DNA damage were observed in tumour cells than in spleen and marrow cells of mice exposed to 10-100 mg/kg tirapazamine, consistent with the presence of hypoxic cells and the greater bioreductive capacity of tumours. In mice injected with 25-200 mg/kg RSU 1069, aerobic cells exhibited large numbers of SSBs while toxic DNA interstrand crosslinks were produced only in hypoxic cells. Cells from bone marrow and spleen showed extensive numbers of SSBs, but minimal crosslinking compared to tumours where 10-20% of cells were heavily crosslinked. DNA damage produced by these two bioreductive drugs may be useful in estimating the range of individual cell oxygen contents within tumours and normal tissues.     

Therapeutic effects of combination of paeoniflorin and albiflorin from Paeonia radix on radiation and chemotherapy-induced myelosuppression in mice and rabbits

The aim of this study was to investigate the therapeutic effects of the combination of paeoniflorin and albiflorin (CPA) extracted from Paeonia radix on radiation and chemotherapy induced myelosuppression in two animal models: mice and rabbits. Mice were exposed to X-ray radiation (400 Roentgen), and both mice and rabbits were intraperitoneally injected with cyclophosphamide (100.0 mg/kg) and cytarabine chloride (92.7 mg/kg), respectively, for 3 days to induce myelosuppression. CPA was subsequently administrated intravenously at low (15.0 mg/kg for mice, 6.00 mg/kg for rabbits), intermediate (30.0 mg/kg for mice, 12.0 mg/kg for rabbits) and high (60.0 mg/kg for mice, 24.0 mg/kg for rabbits) doses, as well as orally (60.0 mg/kg for mice, 24.0 mg/kg for rabbits) for 7 days. Shenqi tablets were used as positive controls (oral administration of 936.0 mg/kg for mice, 336.0 mg/kg for rabbits). The administration of CPA significantly ameliorated myelosuppression in all cases. For the X-ray irradiated mice and the chemotherapy treated mice and rabbits, high dosages of CPA resulted in the recovery of, respectively, 94.4%, 95.3% and 97.7% of hemoglobin content; 67.7%, 92.0% and 94.3% of platelet numbers; 26.8%, 137.1% and 107.3% of white blood cell counts; as well as a reversal in the reduction of peripheral differential white blood cell counts. There was also a recovery of 50.9%, 146.1% and 92.3%, respectively, in the animals' relative spleen weight. Additionally, a recovery of 35.7% and 87.2% in the number of bone marrow nucleated cells was observed in the radio- and chemotherapy treated mice, respectively. Bone marrow white blood cell counts also resumed to normal levels. These results substantiate the marked therapeutic effects of CPA to ameliorate myelosuppression induced by radio and chemotherapy.     

睡莲花烟花苷对半乳糖胺致小鼠急性肝损伤的保护作用

目的：研究睡莲花烟花苷对D-半乳糖胺（D-Gal）所致小鼠急性肝损伤的保护作用。方法：将60只昆明小鼠随机分为正常组,模型组,阳性对照联苯双酯组,烟花苷（25、50和100 mg/kg）给药组,共6组,每组10只。阳性对照联苯双酯组和烟花苷给药组按10 mL/kg每日灌胃给药1次,正常组和模型组每日灌胃等体积蒸馏水,连续灌胃7 d,末次给药1 h后,正常组小鼠腹腔注射生理盐水0.02 mL/g,其他各组腹腔注射D-Gal（800 mg/kg,按0.02 mL/g）造模。造模8 h后摘眼球取血,测定血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）、白细胞介素IL-1β（IL-1β）、白细胞介素（IL-6）、肿瘤坏死因子α（TNF-α）和干扰素γ（INF-γ）水平。颈椎脱臼处死小鼠,摘取肝脏、脾脏称取质量,计算脏器系数,取0.3 g肝组织制备匀浆,检测肝匀浆中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH）及一氧化氮（NO）含量。并取肝左叶距边缘0.5 cm处小块组织,进行肝组织病理学检查。结果：与模型组比较,烟花苷在（50、100 mg/kg）剂量时,小鼠血清ALT和AST水平均显著降低（P均 < 0.01）,血清中促炎因子IL-1、IL-6、TNF-α和INF-γ水平降低（P < 0.05）;肝脏、脾脏系数降低（P < 0.05）,肝匀浆中SOD和GSH活力均显著升高（P均 < 0.05）,MDA和NO含量均显著降低（P均 < 0.05）;肝病理检查结果显示与模型组比较,烟花苷各剂量组肝细胞损伤程度明显减轻,炎性细胞浸润显著减少,其中烟花苷50和100 mg/kg组较25 mg/kg组受损程度较轻、修复情况较好。结论：烟花苷对D-Gal致小鼠急性肝损伤具有保护作用,其作用与促进抗氧化酶、抑制促炎因子的表达有关。     

Effects of a Combination of Cyclophosphamide and Human Recombinant Interleukin 2 on Pulmonary Metastasis after the Surgical Removal of a 3-Methylcholanthrene-induced Primary Tumor in Autochthonous Mice

We have investigated the therapeutic effects of a combination of cyclophosphamide (CY, 150 mg/kg, iv) and human recombinant interleukin 2 (IL-2, 5 × 10⁴ JU/day, ip for 5 days) on autochthonous tumors induced in mice by 3-methylcholanthrene. The initial treatment was carried out when the tumor had reached 8 to 10 mm in diameter. Twenty-eight out of 35 mice (80%) died of local recurrence and pulmonary metastasis of tumor cells within 53 × 40 days (mean survival time, MST × SD) after the surgical removal of the primary tumor. When these mice were treated with both CY and IL-2 following the operation (Op), only 10 out of 20 mice (50%) died of recurrence and metastasis. The survival rate, however, was not improved by CY chemotherapy alone or IL-2 immnnotherapy alone, although each provided a prolongation of the MST. Natural killer cell and LAK precursor cell activities in the spleen cells from the treated mice were found to be restored by IL-2 alone or CY + IL-2, whereas they were suppressed by CY alone. These findings reveal that the restoration of the antitumor activity of spleen cells does not provide an improved therapeutic effect by itself and that IL-2 immunotherapy requires the associated effect of CY chemotherapy to achieve an improved therapeutic effect.