抗诱变中草药的配伍研究

目的：选择具有抗诱变作用的中草药进行配伍，筛选出抗诱变作用最佳的配伍方案，用于肿瘤的预防。方法：根据诱变剂敏感性与肿瘤易感性的关系的理论，通过增强染色体的稳定性来降低肿瘤易感性。采用诱变剂敏感性实验方法，用博莱霉素作为诱变剂，将不同剂量的具有抗诱变作用的中草药组合成配伍，采用L9(3^4)正交表进行实验，以染色体断裂率为效应指标，观察各剂量组合的配伍的抗诱变效果。结果：经极差分析，配伍中各中草药主次因素排列为。最佳配比A1B3C3D1。结论：对诱变剂敏感的人群，可用此配伍增加染色体对诱变剂的拮抗作用，而增加染色体的稳定性。     

黄芪对环磷酰胺诱发小鼠骨髓嗜多染红细胞微核的影响

本文用小鼠骨髓嗜多染细胞微核细胞，研究了黄芪水提物对诱变剂环磷酰胺的抗或去诱变作用。结果表明：对大剂量ＣＰ诱发的微核，未发现黄芪有明显的抑制作用，但是对低剂量ＣＰ诱发的微核形成具有明显抑制作用；其作用机理主要是抗诱变作用而并非去诱变作用；黄芪对高剂量诱变原的抗诱变作用，主要表现在促进ＤＮＡ修复或诱变原排出等方面。     

芦荟大黄素及芦荟提取物的诱变性和抗诱变性

目的:用L5178Y小鼠淋巴瘤细胞体外微核试验评价芦荟大黄素和芦荟提取物的诱变和抗诱变作用,为其安全性评价提供依据。方法:设溶剂对照、阳性对照和抗诱变对照,芦荟大黄素和芦荟提取物诱变和抗诱变试验各设4个剂量组,处理L5178Y细胞12 h后按常规方法进行体外微核试验分析。结果:较高浓度(6.67μg/ml)的芦荟大黄素可致微核细胞率增加,与对照组比较,差异有统计学意义(P0.05);而芦荟提取物未见此效应。在一定剂量范围内,芦荟大黄素(0.22～6μg/ml)和芦荟提取物(20～180μg/ml)对甲磺酸甲酯(MMS)所致微核细胞率均有一定程度的拮抗作用,与对照组比较,差异有统计学意义(P0.01)。结论:芦荟大黄素具有一定的诱变作用,而在本实验剂量范围内的芦荟提取物未见遗传毒性。两种受试物在一定范围内均能较好地拮抗MMS所致的染色体损伤。     

硒与抗坏血酸在SCE和UDS试验中的抗诱变效应

通过离体和整体实验方法观察，发现随着经饮水摄入的Vc和／或Se剂量的增大，诱变物MNNG诱发的小鼠骨髋细胞SCE数下降，且呈剂量反应关系；同时Vc与Se单独或联合使用均可明显降低MNNG诱发的人全血细胞培养的UDS值。结果提示Vc和Se具有抗诱变协同效应。实验还显示Se和Vc作为抗诱变剂，本身在高剂量下又呈现遗传毒性。     

Evaluation of mutagenicity and anti-mutagenicity of aloe-emodin and aloe extract

目的:用L5178Y小鼠淋巴瘤细胞体外微核试验评价芦荟大黄素和芦荟提取物的诱变和抗诱变作用,为其安全性评价提供依据.方法:设溶剂对照、阳性对照和抗诱变对照,芦荟大黄素和芦荟提取物诱变和抗诱变试验各设4个剂量组,处理L5178Y细胞12h后按常规方法进行体外微核试验分析.结果:较高浓度(6.67μg/ml)的芦荟大黄素可致微核细胞率增加,与对照组比较,差异有统计学意义(P＜0.05);而芦荟提取物未见此效应.在一定剂量范围内,芦荟大黄素(0.22～6μg/ml)和芦荟提取物(20～180μg/ml)对甲磺酸甲酯(MMS)所致微核细胞率均有一定程度的拮抗作用,与对照组比较,差异有统计学意义(P＜0.01).结论:芦荟大黄素具有一定的诱变作用,而在本实验剂量范围内的芦荟提取物未见遗传毒性.两种受试物在一定范围内均能较好地拮抗MMS所致的染色体损伤.     

抗诱变和诱变同步快速试验方法的研究

快速筛选抗诱变剂和诱变剂对控制环境致癌因素及肿瘤预防具有重要意义,为此我们据SOS反应原理研究了四种同步试验方法均取得了满意的结果。以0.05mg/ml的丝裂震素C(MMC)和0.004mg/ml的平阳霉素为阳性诱变指示剂;100mg/ml维生素C(Vitc)为已知抗诱变指示剂;以生理盐水为既不抗诱变又无诱变性的阴性对照剂。标准菌株、培养基制作、菌种活化及处理、加菌铺皿等操作与原噬菌体诱导试验相同。用以下四种方式加试剂进行抗诱变及诱变同步试验:     

应用微核试验研究四种蔬菜的抗突变性

本文目的在于探讨蔬菜混合成分在活体内有无抗阳性致突物环磷酰胺(CP)的诱变活性作用。研究方法选择小鼠骨髓细胞微核试验,用新鲜菜汁及它们的干蔬菜苯:甲醇有机提取物观察四种蔬菜(菜花、白菜、黄瓜、芹菜)在哺乳动物体内对染色体诱变剂CP诱导的染色体损伤的抑制作用。结果表明四种蔬菜新鲜菜汁对经腹腔注射剂量为30mg/kgCP后的小鼠立即经口灌胃,其剂量     

几种中草药及绿茶对B(a)P和NNK的抗诱变作用

目的: 探讨绿茶、茶多酚、半枝莲、白花蛇舌草及犀黄丸等的水溶性提取物对苯并芘[B(a)P]和4-甲基亚硝胺基-1-(3-吡啶基)-1-丁酮(NNK)的抗诱变作用. 方法: 采用沙门氏菌回变试验(Ames试验). 结果: 除各受试物的最小剂量组外,其它浓度的绿茶、茶多酚、半枝莲、白花蛇舌草及犀黄丸等均具有明显的抑制B(a)P和NNK诱发TA 98和TA 100回复突变的作用.经统计学处理,各试验组与对照组比较有显著性差异(P<0.01). 结论: 受试的中草药和绿茶对B(a)P和NNK均有抗突变作用,且存在剂量反应关系.     

Trad—MCN分析中引入多微核四分体率

在Ｔｒａｄ－ＭＣＮ分析中，以微核率作指标来判断环境诱变剂对染色体的损伤程度和诱变剂量强弱一直沿用至今，本文用实验证明了当作物中存在有诱变剂镉的阻遏剂，如维生素Ｅ或褐藻酸钠时，单一微核率指标已不足以反映出诱变剂的强度与剂量大小，更不能反映诱变剂与阻遏剂间的作用及其程度，因此，作者建议应将多微核四分体率作为一项重要指标引入Ｔｒａｄ－ＭＣＮ分析中，与微核率一道共同反映在研究工作中。     

辐射所致残存染色体易位与放射敏感性关系研究

目的 :应用荧光原位杂交 (FISH)方法研究人肿瘤细胞放射敏感性与染色体残存易位关系及临床应用的可行性。方法 :采用 3种放射敏感性不同的人肿瘤细胞系 :鼻咽鳞癌 (CNE)、肺腺癌 (SPC)和乳腺腺癌 (MCF 7)。通过克隆形成方法测定 2Gy、4Gy、6Gy和 8GyX线照射剂量下肿瘤细胞的存活率。采用常规染色体制片过程和 2号染色体涂染探针及FISH方法 ,测定 2Gy、4Gy和 6GyX线照射2 4h后 ,肿瘤细胞 2号染色体内在和诱导的畸变量。结果 :未照射的对照细胞 2号染色体存在不同程度的内在畸变。 2Gy、4Gy和 6Gy照射后 2 4h ,CNE、SPC和MCF 7细胞诱导生成的残存染色体畸变与剂量关系一致 ,能够反映细胞的放射敏感性 ,所有细胞系诱导 2号染色体生成的畸变与细胞存活率均存在良好相关性 (rs=0 96)。结论 :诱导的残存染色体畸变与照射剂量呈线性关系 ,采用FISH方法计数照射诱导的残存染色体畸变 ,可以预测肿瘤细胞间的放射敏感性差异并具有重要的临床意义     

两种中草药抗癌有效部位的抗血管生成作用研究

 目的 对在中医理论上具有活血化瘀功效且有抑瘤作用的单味中草药6号和10号药的有效部位T3和M2进行抗血管生成作用研究。方法 体外培养人血管内皮EC细胞MTT实验和鸡胚绒毛尿囊膜（CAM）实验。结果 T3和M2对人血管内皮EC细胞有明显的抑制增生的作用（P＜0.05），抑制率与药物形成较好的浓度梯度关系。CAM实验T3（1 g／ml，3 μl）作用部位的血管结构破坏，血液溢出，周围血管网减少；M2（4 g／ml，3 μl）作用部位小血管网减少，对周围的大血管有一定的聚敛、趋化作用。结论 有活血化淤功能的中草药6号和10号药的抗癌有效部位T3和M2的抗癌机制之一可能是抗血管生成。     

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.     

广东省居民饮用凉茶及煲汤与鼻咽癌发病关系的流行病学研究

目的:探讨在广东鼻咽癌高发地区居民饮用凉茶及煲汤与鼻咽癌发病的关系,为制定高发区鼻咽癌预防措施提供依据。方法:选取广东肇庆地区在2010年至2013年新诊断的1 245例鼻咽癌为病例组。并按照居住地、性别、年龄为匹配条件,选取同时期1 293名健康对照。开展包括饮用凉茶及煲汤在内的生活饮食习惯的问卷调查。采用单因素以及多因素Logistic回归分析,计算各生活环境因素与鼻咽癌发病风险的比值比（odds ratio,OR）。结果:凉茶与煲汤与鼻咽癌的发病风险呈负相关。与不饮用凉茶人群相比,每年饮用凉茶与每月饮用凉茶的人群其发病风险均降低,OR值分别为0.65和 0.74;与不煲汤的人群相比,煲汤频率为每月一次以及每周一次时,其OR分别为0.55与0.51,P＜0.05。进一步对30种煲汤常用中药材进行调查,发现有7种具有保护作用,其中中药花旗参的保护作用最明显,其OR=0.18, 95%CI:0.05~0.73。结论:广东地区居民经常饮用凉茶及煲汤可降低鼻咽癌的发病风险,煲汤中的部分中药材的使用可能成为预防鼻咽癌的有效措施。     

藤黄Ⅱ号抗癌作用的实验研究

藤黄Ⅱ号是从传统中药藤黄中提取的新的抗肿瘤有效成分,药理实验表明:本品对小鼠白血病L1210的抑制作用优于藤黄酸,对艾氏腹水癌,P388,ARS腹水及Lewis肺癌等实体瘤亦有明显抑制作用,和马蔺子甲素及放射合用,可明显增加对小鼠宫项癌U14的疗效。腹腔注射及口服藤黄Ⅱ号,对La795肺腺癌的肺转移亦有明显抑制作用。     

中药防治肝癌化疗栓塞术后肝储备功能损害的临床研究

背景与目的:肝癌化疗栓塞术(Transcatheterarterialchemoembolization,TACE)可引起肝储备功能下降。探讨中药预防和治疗肝癌TACE后肝储备功能的损害。方法:61例中晚期肝癌患者随机分成中西医治疗组(n=30)和西医治疗组(n=31),两组在TACE后均予西药常规护肝治疗及对症处理,中西医治疗组在TACE前、后加服用健脾活血为主的中药,再根据TACE后出现的症状对症选药。两组病例分别在第一、第二次TACE治疗前和第二次TACE治疗后一个月各检查吲哚靛青绿15分钟潴留率(RetentionRateofIndocyanineGreenat15Minutes,ICGR15)。结果:第一次TACE前ICGR15:中西医治疗组11.18%±7.30%,西医治疗组11.83%±7.18%,P>0.05;第二次TACE前ICGR15:中西医治疗组11.69%±5.13%,西医治疗组16.64%±10.15%,P<0.05;第二次TACE后一个月ICGR15:中西医治疗组为11.53%±5.30%,西医治疗组19.80%±11.26%,P<0.05。结论:健脾活血中药可防治肝癌TACE后所引起的肝储备功能损害。     

Deletion in poly(ADP-ribose)polymerase pseudogene and lung cancer risk

The poly(ADP-ribose)polymerase (PADPRP) gene has been implicated in carcinogenesis through its role in DNA repair, replication and recombination. A two-allele polymorphism in the chromosome 13 PADPRP pseudogene has been studied in several racial groups. It has been suggested that the B allele, which results from a 193-bp deletion in the gene, predisposes to myeloma in Blacks. We assessed the association between chromosome 13 PADPRP pseudogene genotype, mutagen sensitivity (a marker reflecting host DNA repair capability), cigarette smoking, and lung cancer risk in a minority lung cancer case-control study. The chromosome 13 PADPRP pseudogene polymorphism was detected by polymerase chain reaction-based analysis. Mutagen sensitivity was measured by an in vitro assay that quantified bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. We examined 121 cases (80 African- Americans and 41 Mexican-Americans) with previously untreated lung cancer and 171 matched controls. Our results suggested that the distribution of the PADPRP pseudogene genotype frequencies was significantly different among African-American and Mexican-American controls (P < 0.001). The susceptibility genotype (i.e. at least one B allele) was found in 82.5% of African-American cases, 79.4% of African- American controls, 53.7% of Mexican-American cases, and 32.4% of Mexican-American controls. The odds ratios (OR) and 95% confidence intervals for the PADPRP susceptibility genotypes were 2.3 (95% CI = 0.7-8.0) and 3.2 (95% CI = 1.0-10.3) for African-Americans and Mexican- Americans respectively, after adjustment by age, sex, pack-years and mutagen sensitivity. Patients with the susceptibility genotype appeared to have more mutagen-induced breaks than did patients with the other genotype. Only adenocarcinoma was significantly associated with the PADPRP susceptibility genotype (OR = 3.8). Mutagen sensitivity (> or = 1 break/cell) was significantly associated with lung cancer risk for both ethnic groups with increased ORs of above three-fold. On stratified analysis, synergistic interactions were noted for the PADPRP susceptibility genotype, mutagen sensitivity and smoking status. In Mexican-Americans, the ORs for PADPRP susceptibility genotype, mutagen sensitivity and both risk factors combined were 1.3, 2.7 and 17.1 respectively. The combined OR for the PADPRP susceptibility genotype and smoking status was 15.6. Therefore, this polymorphism appears to be associated with lung cancer risk. However, it is likely that no single genotype is sufficiently predictive of risk and that a panel of susceptibility markers is needed to define the high-risk subgroup.      

中药合剂"振明正生"对三株人肿瘤细胞裸鼠移植瘤抑制作用的观察

目的:观察中药合剂"振明正生"(ZMZS)对人肿瘤细胞的抑制作用.方法:BALB/c裸鼠分别接种人白血病细胞系(K562)、鼻咽癌细胞系(CN1)和胰腺癌细胞系(P3),2×106/只.接种后24小时开始给药,实验组裸鼠每天口服中药合剂0.2ml/只,连续4周.对照组裸鼠口服生理盐水0.2ml/只.每周测量动物肿瘤大小,计算肿瘤生长抑制率.结果:经过3或4周的治疗,中药合剂"振明正生"对K562、CN1和P3有明显抑制作用.结论:中药合剂"振明正生"对三株人肿瘤细胞裸鼠移植瘤有显著的治疗效果.     

骨髓增生异常综合征的治疗探索与展望

 【摘要】　骨髓增生异常综合征（MDS）是一组起源于造血干／祖细胞的获得性、克隆性、异质性疾患。中国与西方国家MDS患者具有不同的遗传学特征。以砷剂青黄散为主治疗MDS已取得肯定临床疗效。疗效机制研究表明含砷中药治疗不能改变MDS患者已有的染色体异常,但MDS患者异常增高的甲基化显著减低,含砷中药治疗的主要作用机制是去甲基化。血砷浓度测定表明有效血砷质量浓度为（19.39±10.36）μg／L,明显低于砷剂治疗急性早幼粒细胞白血病所需血砷浓度。进一步研究砷剂的去甲基化机制、进行个体化血砷浓度检测和疗效关系的研究是今后研究的方向。     

Evidence of a chromatin basis for increased mutagen sensitivity associated with multiple primary malignancies of the head and neck

Individuals at increased risk for cancer development have been reported to exhibit increased mutagen sensitivity as detected by the G₂ phase chromosome breakage assay. To better understand the basis for such chromosome sensitivity, we examined 4 lymphoblastoid cell lines derived from 4 head and neck cancer patients, 2 of whom were previously shown to have normal bleomycin sensitivity and 2 high bleomycin sensitivity (and multiple primary tumors). These cell lines were studied for cell survival and initial damage and repair at both the DNA and chromosome levels, and the results compared to a normal control cell line and 3 ataxia telangiectasia homozygote cell lines. While all cell lines exhibited nearly equal levels of initial DNA damage and repair throughout the cell cycle, both the ataxia telangiectasia homozygote cell lines and 2 cell lines derived from individuals with multiple head and neck primary tumors showed increased levels of initial chromosome damage (detected by premature chromosome condensation), a reduced fast repair component and higher residual chromosome damage. Our results suggest that one component of the enhanced mutagen sensitivity phenotype observed in cancer-prone individuals may involve an inherent chromatin alteration that allows a more efficient translation of DNA damage into chromosome damage following mutagen exposure. The degree of such an alteration might then be associated with an increased risk for second primary tumors in other carcinogen-exposed sites. © 1995 Wiley-Liss, Inc.