环氧乙烷遗传毒性的研究V.亚慢性吸入环氧乙烷的小鼠骨髓细胞…

本文观察环氧乙烷（ＥＴＯ）亚慢性吸入染毒小鼠（５４ｍｇ／ｍ＾３，３６０ｍｇ／ｍ＾３，２ｈ／ｄａｙ，６ｄ／ｗｋ，１４ｗｅｅｋ）骨髓细胞染色体结构畸变率显著高于正常对照组（４．２％Ｐ〈０．０１），５４ｍｇ／Ｍ＾３染毒组未见显著性差异。此外，发现两组染毒小鼠骨髓细胞分裂相明显少于正常对照组，３６０ｍｇ／ｍ＾３浓度组细胞分裂抑制效应大于５４ｍｇ／ｍ＾３浓度组，细胞分开受抑制的机理尚待探讨。     

环氧乙烷的遗传毒性研究IV.小鼠骨髓细胞染色体畸变亚急性试验

以４组小鼠各１０只为一组，分别给予ＥｔＯ吸入剂量为５４，１８０，５４０ｍｇ／ｍ＾３２ｈｒ／ｄ连续５天。观察了ＥｔＯ对小鼠骨髓细胞染色体畸变的畸变率，发现总畸变率分别为０．５，１．２，３．２，７．０％，高浓度（５４０ｍｇ／ｍ＾３）中等浓度（１８０ｍｇ／ｍ＾３）二组与对照组比较有统计显著性差异；而低浓度（５４ｍｇ／ｍ＾３）组与对照组比较无显著差异。结果表明ＥｔＯ使小鼠骨髓细胞分裂中的染色体畸变，主要为     

环氧乙烷的遗传毒性研究Ⅳ．小鼠骨髓细胞染色体畸变亚急性试验

以４组小鼠各１０只为一组,分别给予ＥｔＯ吸入剂量为５４,１８０,５１Ｏｍｇ／ｍ３２ｈｒ／ｄ连续５天,观察了ＥｔＯ对小鼠骨髓细胞染色体畸变的畸变率,发现总畸变率分别为０．５,１．２,３．２,７．Ｏ％,高浓度（５４０ｍｇ／ｍ３）、中等浓度（１８０ｍｇ／ｍ３）二组与对照组比较有统计显著性差异;而低浓度（５４ｍｇ／ｍ３）组与对照组比较无显著差异。结果表明ＥｔＯ使小鼠骨髓细胞分裂中的染色体畸变,主要为裂隙、断裂及断片,且随着浓度的增加而加剧。     

环氧乙烷的遗传毒性研究Ⅱ.小鼠精子畸形试验

本文用亚急性和亚慢性２种处理方法，观察了（ｅｔｈｙｌｅｎｅｏｘｉｄｅ，Ｅｔｏ）对小鼠精子畸形的诱变率，发现亚急性处理组只有高浓度（５４０ｍｇ／ｍ）第７ｄ取材的与对照组比较有显著的诱变率（１５２±７６．２７Ｐ＜０．０１），且具明显的剂量─效应关系；而大于７ｄ的以及其它各种浓度的处理与对照组相比均无显著差异．但亚慢性处理组连续１４ｗｋ的吸入，其低浓度（５４ｍｇ／ｍ３）与高浓度（３６０ｍｇ／ｍ３）的吸入与对照组比较，都有明显的诱变率（分别为２９．４±ｌ６．２４，Ｐ＜０．０５和５２．９１±１１．９７，Ｐ＜０．００１）。结果表明小剂量长期吸入造成的诱变性明显，也比较符合化工工人长期操作接触化学物剂量的实际悄况，特别对男性工人接触Ｅｔｏ后引起对后代的致畸或不育症的潜在可能性更应予以关注及进一步研究。     

三种毒物对小鼠受精卵染色体畸变的影响

本文采用小鼠受精卵染色体分析方法，对敌枯双、重铬酸钾、二硫化碳三种毒物的生殖细胞遗传物质诱变作用进行了评价，结果证明阴性对照组染色体数目畸变细胞率为９．Ｏ％，与各染毒组比较均有显著差异，敌枯双组为５１．８％，（Ｐ＜０．０１）；重铬酸钾组为３３．８％，（Ｐ＜０．０１）；二硫化碳（１０ｍｇ／ｍ３）组为２２．８％，（Ｐ＜０．０１），（１００ｍｇ／ｍ３）组为２｝８％，（Ｐ＜０．０１）。     

维生素C对苯致小鼠骨髓细胞P53表达拮抗作用的研究

目的：探讨维生素Ｃ对苯致小鼠骨髓细胞Ｐ５３表达的影响。方法：采用静式吸入染毒的方法,共染毒３ｄ,并在其饮水中加入一定量的维生素Ｃ,用免疫组化方法测定小鼠在细胞Ｐ５３阳性率,并作Ｕ检验。结果：染毒３０ｄ后无一小鼠死亡,白细胞计数也在正常范围内,而ＰＣ５３表达则是最高浓度组高于对照组和其他染毒组（Ｐ〈０．０１或Ｐ〈０．０５）;维生素Ｃ摄入量每日每只小鼠在２．５ｍｇ以上可降低Ｐ５３表达阳性率;加入时间在染毒期２／３以上时也可降低Ｐ５３表达阳性率。结论：苯吸入对小鼠的骨髓细胞ＤＮＡ有一定的影响,维生素Ｃ具有一定的拮抗作用。     

苯,甲苯,二甲苯对小鼠早期精细胞的微核效应

本文用简化Ｔａｔｅｓ微核试验法检测了苯、甲苯和二甲苯对小鼠睾丸生殖细胞的诱变性，用不同浓度的苯（４．５ｇ／ｍ３，９．０ｇ／ｍ３）、甲苯（２．５ｇ／ｍ３，５．０ｇ／ｍ３和二甲苯（２．５ｇ／ｍ３，５．０ｇ／ｍ３）分别经呼吸道对小鼠染毒，连续３天。于染毒首日后第１５天杀鼠制片，测得微核率６．８‰，７．２‰，３．０‰，２．４‰，３．４‰、４．０‰。这表明苯和二甲苯（５．０ｇ／ｍ３组）所致早期精细胞微核率明显高于阴性对照组（１．６‰），有统计学意义（ｐ＜０．０１或Ｐ＜０．０５），可认为是雄性生殖细胞染色体断裂剂。根据开始染毒到杀鼠制片的间隔时间判断，苯和二甲苯主要作用于减数分裂前的Ｇ１或Ｓ期初级精母细胞。     

醋酸铅,氯化汞对小鼠精子染色体畸变及其受精卵发育的影响

分别用醋酸铅（１ｍｇ／ｋｇ·ｗｔ）和氯化汞（Ｏ．５ｍｇ／ｋｇ·ｗｔ）给雄性性成熟昆明种小鼠染毒，共染毒７０天，然后用染毒雄性小鼠与非染毒雌性小鼠交配，取受精卵观察卵发育状况并制备受精卵染色体。结果表明，醋酸铅染毒组（２６．８％）和氯化汞染毒组（３６．４％）受精卵发育异常率，均明显高于非染毒组（１３．３％）（Ｐ＜０．０１）。两组精子染色体数目异常率（１１．９８％和１０．８０％）也高于非染毒组（８．６３％）。但无统计学差异（Ｐ＜０．０５）。     

绞股蓝多糖（GPS）生物学作用的研究

本文报道绞股蓝多糖（ＧＰＳ）的生物学作用－抗氧化作用、细胞免疫促进作用。实验结果表明：（１）ＧＰＳ５ｍｇ／只／天灌胃，能降低正常小鼠脂质过氧化（ＬＰＯ）水平（Ｐ〈０．０５），能提高正常小鼠超氧氧化物歧化酶（ＳＯＤ）活性（Ｐ〈０．０５）。（２）ＧＰＳ５０ｍｇ／只／天灌胃，能显著降低亚急性衰老模型小鼠脂质过氧化水平（Ｐ〈０．０１），能显著提高亚急性衰老模型小鼠超氧化物酶活性（Ｐ〈０．０１），（３）ＧＰ     

DDNAQ致突变作用的研究

本研究对某厂１２２名接触１─〔２．４─二硝基〕苯氧基—５—〔３．４—二硝基〕苯氧基—４．８—二硝基蒽醌（ＤＤＮＡＱ）（车间空气粉尘浓度为０．１６ｍｇ／ｍ３）的工人和某厂１００名非接触工人进行了口腔粘膜上皮细胞微核检查，发现接触组微核人员出现率和平均微核率分别为７６．２２％和２％，显著高于非接触组相应的３０．００％（Ｐ＜０．０１）和０．４％（Ｐ＜０．０１）。是时，上述接触组和非接触组各１２名工人进行了中性白细胞ＤＮＡ含量测定，接触组（６００个细胞）ＤＮＡ含量为３．６７±０．３０，与非接触组（６００个细胞）的３．０２±０．１８相比较，差别显著（Ｐ＜０．０１）。此外，动物实验结果表明，小鼠受精卵染色体数目畸变细胞率，染毒组（０．８ｍｇ／ｋｇ·ｗｔ）为１８．７５％，显著高于对照组的８．７４％（Ｐ＜０．０５）；金黄地鼠胚胎早期培养细胞转化试验，染毒组（０．１ｕｇ／ｍｌ，１．０ｕｇ／ｍｌ转化克隆／总克隆为４／４６７、３／４４２（空白对照组为０／５０８），呈阳性结果。上述结果说明ＤＤＮＡＱ对遗传物质存在作用，应加强职业性接触工人卫生防护工作，保护工人及其后代的健康。     

小鼠慢性吸入70号汽油对骨髓细胞染色体及微核损伤的实验研究

给小鼠吸入７０号汽油３０ｄ，６０ｄ，９０ｄ，动态观察了不同剂量的汽油对小鼠骨髓细胞染色体畸变及微核的影响。结果小鼠吸入汽油９０ｄ，在剂量为１０００ｍｇ／＾３的浓度下，染色体畸变率与阴性对照有非常显著差异；而小鼬有髓嗜多染红细胞微核试验在小鼠吸入汽油６０ｄ时高剂量下，９０ｄ的中剂量，高剂量下与阴性对照有显著性差异。     

38. Morphological Changes of Testis and Sperm Subchronic Inhalation of Ethylene Oxide in Mice

Male mice were exposed to ethylene oxide(Et0) at concentrations of 54, 360 mg/m3 for two hours a day, on six days a week for 14 weeks. The results of sperm abnormalities test in mice showed the mutation frequencies of both low (54 mg/m3) and high (360 mg/m3) concentration groups are abvious (They are 29.40±16.24, P<0.05 and 52.91±11.97, P<0.001, respectively.). These showed that it causes evident mutagenesis to inhale ethylene oxide for a long time although in the low concentration. In light microscopic observation of the testis, the numbers of germ cells and layers of seminiferous epithelium decreased slightly in 54 mg/m3 group, but obviously in 360 mg/m3 group. Sometimes multinucleated giant cells were observed in the damaged seminiferous tubules, and more changes could be seen in the examination of seminiferous tubules under an electron microscope. The changes are: acrosomes of a lot of spermatid during spermiogenesis developmented teratoid and have not had a marked deviation of the hooked acrosome from the long axis of the nucleus, which is a charater of a sperm in mice; excessive nucleoplasm of sperm is eliminated incompletly; autolysis in a lot of spermatid was observed in development; mitochondria which located around the tails of sperm decreased and even disappeared. These abnormal ultrastructures on morphology in spermatogenesis associated the results of Sperm Abnormalities Tests, Dominat-Lethal Tests and Heritable Translocation Tests and so on, which are studied in cytogenetic, explained that Eto is a potent antispermatogenic agent and a teratogen. Indeed, the possiblility of inferti-lity and the teratogenesis in offspring among male workers potentially exposed to Eto should be studied further.     

Autologous bone-marrow transplantation for Burkitt's lymphoma: marrow purging with anti-Y 29/55 monoclonal antibody and complement

Reinfusion of undetected tumour cells is a possible cause of relapse after autologous bone-marrow transplantation. In this paper, a system for in-vitro purging of bone marrow is presented which involves the B-cell neoplasia-associated monoclonal antibody anti-Y 29/55 and complement. Five patients with Burkitt's lymphoma were transplanted with purged marrow, demonstrating the clinical feasibility of the method. The pretransplant regimen included vincristine 2 mg/m2, adriamycin 60 mg/m2, four doses of cyclophosphamide 45 mg/kg and total body irradiation with 6 Gy. Tumour control appears to be better in patients with purged bone marrow as compared to an earlier patient group with unpurged marrow.     

亚砷酸联合GDP方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的：观察亚砷酸（三氧化二砷,As2O3）联合GDP方案（吉西他滨,顺铂,地塞米松）治疗难治性或复发性非霍奇金淋巴瘤（non-hodgkin＇s lymphoma,NHL）的有效率。方法：23例难治性或复发性非霍奇金淋巴瘤（NHL）,给予吉西他滨1000mg/m2,第1和第8天,顺铂25mg/m2第1-3天,地塞米松20mg/m2,第1-5天,As2O310mg/d,第1-14天。21天为1个周期。结果：完全缓解9例,部分缓解6例,总有效率65.22%。肿瘤中位进展时间6个月,1年生存率39.13%。不良反应主要为血液学毒性。结论：亚砷酸联合GDP方案是治疗难治性或复发性非霍奇金淋巴瘤较为安全有效的化疗方案。     

Effect of high dose etoposide, adriamycin, cisplatin (EAP) therapy with autologous bone marrow transplantation in gastric cancer

A clinical usefulness of high dose EAP therapy with autologous bone marrow transplantation for gastric cancer was investigated. Three patients with advanced gastric cancer (one recurrent and 2 inoperable) with measurable lesions were treated with high dose EAP therapy consisting of VP-16 1200 mg/m2, ADM 80 mg/m2 and CDDP 80-120 mg/m2, and then 1 x 10(7)/kg of cryopreserved autologous bone marrow cells were transfused intravenously. All patients were recovered from aplastic period without any severe complications. Measurable lesions, namely, stenosis of prepyloris lesion, lymph node metastasis and invasion into pancreas in 3 patients with gastric cancer were reduced or diminished. It seemed that high dose EAP therapy with autologous bone marrow transplantation was safe and an useful strategy, especially for advanced gastric cancer.     

肝脂素(YS2H)对体外人白血病细胞及基质细胞生长影响的研究

目的：研究肝脂素（YS2H）对人白血病细胞及基质细胞生长的影响。方法：采用白血病祖细胞集落生长方法、^3H-TdR掺入法,观察YS2H对25例急性髓细胞白血病患者的骨髓白血病细胞作用;采用骨髓基质细胞培养法观察经YS2H作用,培养4周时的正常人及白血病患者骨髓基质细胞形态变化。结果：YS2H对体外人的急性髓细胞白血病细胞有明显的生长抑制作用,存在剂量依赖关系,而对正常骨髓CFU－GM集落形成影响不大（P＞0．05）;同时发现,YS2H可使基质细胞悬浮液中的白血病细胞及集落数减少,并使白血病的骨髓基质细胞形态趋向正常骨髓基质细胞形态。结论：YS2H是一种有选择性抑制白血病细胞生长的脂类抗白血病药物,具有临床研究应用价值。     

Long-term effect of homoharringtonine on chronic granulocytic leukemia

From 1996, low-dosage (1.5 mg/m2) homo- harringtonine (HHT) was used to treat chronic granulocytic leukemia in chronic phase (CGL-CP) patients for remission induction and long term maintenance treatment. It was found that the period of chronic phase intervals was longer in low-dosage HHT group than that in hydroxyurea (HU) group and HHT could induce apoptosis of bone marrow CD34+ cells from CGL-CP patients. MATERIALS AND METHODS Patients Newly diagnosed CGL-CP patients …     

Clastogenic Potential of Ruta graveolens Extract and a Homeopathic Preparation in Mouse Bone Marrow Cells

Ruta graveolens belonging to family Rutaceae has long been traditionally used as a medicinal plant as well asa flavoring agent in food. However, very little data are available on the toxicity of the plant. This report presentsevidence on the genotoxic and clastogenic potential of an extract of Ruta graveolens and Ruta 200C, a homeopathicpreparation. Various types of chromosomal aberrations were noted in bone marrow cells after treatment. Thepercentage of aberrated cells in 4the 00mg/kgb.wt extract administered group was found to be 21% and with1000mg/kg.b.wt it was 31%. The 23% for the Ruta 200C treated group was also elevated as compared to the3%for untreated animals. In addition, bone marrow cells had higher incidence of micronuclei induction whentreated with the extract (400mg and 1000mg/kg body weight) and 20μl/animal Ruta 200C for 30 days.Administration of the extract (1000mg/kg.b.wt) over a period of 30 days also resulted in damage to cellular DNAas evidenced by comet formation where the comet parameters such as percentage DNA in tail, tail length, tailmoment of the bone marrow cells were increased several fold over control values. The comet tail moment of thebone marrow cells increased from 4.5 ± 2.5 to 50.2 ± 25.2 after the extract treatment. Administration of 20μl/animal Ruta 200C for 5 consecutive days increased the tail moment to 11.7 ± 2.9. These results indicate that Rutagraveolens and Ruta 200C may induce genotoxicity in animals.     

培美曲塞联合顺铂在晚期男性肺腺癌一线治疗中的应用

目的：观察培美曲塞联合顺铂（PP组）与吉西他滨联合顺铂（GP组）作为一线化疗药物治疗晚期男性肺腺癌的疗效及毒副反应.方法：将74例经病理证实的晚期男性肺腺癌患者（Ⅲb和Ⅳ期）分为两组：GP组40例,PP组34例.PP组：培美曲塞500mg/m2,静脉滴注,第1天,持续3-4h;顺铂（DDP） 75 mg/m2,静脉点滴,第1天,每21天为1个周期.GP组：吉西他滨1250mg/m2,静脉点滴,第1、8天;顺铂用法同上,每3周为1个周期.连续4-6个周期.每2周期评价疗效及毒副反应.结果：PP组总有效率[完全缓解（CR）＋部分缓解（PR）]为44.1％,1年生存率为38.2％;GP组总有效率为42.5％,1年生存率为37.5％,两组间总有效率和1年生存率比较均无统计学意义（P＞0.05）.最常见的毒副反应是骨髓抑制和胃肠道反应,其中骨髓抑制两组间比较差异有统计学意义（P＜0.05）.结论：培美曲塞联合顺铂方案可作为一线治疗晚期男性肺腺癌的选择.