农药甲胺基阿维菌素苯甲酸盐的致突变性研究

背景与目的研究甲胺基阿维菌素苯甲酸盐原药是否具有潜在的遗传危害。材料与方法采用Ames试验、小鼠微核试验、小鼠睾丸初级精母细胞染色体畸变试验三种常规方法对其进行致突变性研究。结果各剂量组无论在加或不加S9条件下,其试验菌株的回复突变菌落数均未超过自发回变菌落数的两倍;在试验剂量范围内,各剂量组小鼠骨髓嗜多染红细胞的微核细胞率及小鼠睾丸染色体细胞畸变率与阴性对照组比较差别无统计学意义。结论在本试验条件下,Ames试验、小鼠微核试验、小鼠睾丸初级精母细胞染色体畸变试验均为阴性结果,表明甲胺基阿维菌素苯甲酸盐原药无致突变作用。     

2，4-二氯苯氧乙酸的致突变性研究

目的： 研究2,4-二氯苯氧乙酸(2,4-D)是否具有潜在的遗传毒性。方法：利用Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠睾丸初级精母细胞染色体畸变试验对2,4-D原药的致突变性进行研究。结果：与对照组比较,2,4-D原药各剂量组对TA97、TA98、TA100和TA102菌株均无诱发回复突变菌落数增加的作用(P>0.05),对小鼠骨髓嗜多染红细胞的微核细胞率亦无明显影响(P>0.05),也未引起小鼠睾丸初级精母细胞染色体畸变率明显改变(P>0.05)。结论：在本实验条件下,未发现2,4-D原药的致突变性。     

五氧化二钒对雄性小鼠生殖细胞的突变性研究

目的 :研究钒及其化合物对哺乳动物雄性生殖细胞的致突变性。方法 :本研究选用雄性小鼠 ,用五氧化二钒溶液进行亚急性腹腔注射染毒。剂量为 0 .17mg/kg、2 .13mg/kg、6 .40mg/kg。观察初级精母细胞染色体畸变和早期精细胞微核率。 结果 :三受试组的初级精母细胞染色体畸变率依次为 1.4%、2 .6 % (P <0 .0 5 )、4.2 % (P <0 .0 5 ) ,有剂量反应关系 ,早期精细胞微核率依次为 2 .80‰、4.0 0‰、(P <0 .0 5 )、7.8‰ (P <0 .0 5 ) ,也有剂量反应关系。结论 :研究表明 ,五氧化二钒对哺乳动物雄性生殖细胞具有致突变性。     

中草药保健香烟的减毒及抗突变作用初步研究

背景与目的:探讨中草药保健香烟的降毒作用和抗突变作用.材料与方法:在香烟中加入中草药假(蒟)等制成中草药保健香烟,用该香烟制得生理盐水烟雾液为实验材料,进行小鼠急性毒性实验、小鼠骨髓嗜多染红细胞(PCE)微核试验和Ames试验.结果:小鼠急性毒性实验的半数致死剂量(LD50)保健香烟组比原香烟对照组增加了4～5倍;小鼠骨髓嗜多染红细胞微核率为6‰～10‰,明显低于原香烟对照组(16‰～28‰),并有剂量-效应关系(r=0.9554);Ames试验细菌回变数量比原香烟对照组可减少69%～83%,并同时存在剂量-效应关系(r=0.9843).结论:中草药保健香烟能大幅度降低香烟的毒性和致突变作用.     

特丁净致突变性与蓄积毒性实验研究

【摘要】 背景与目的: 研究特丁净的致突变性与蓄积毒性。 材料与方法: 采用小鼠睾丸精母细胞染色体畸变试验,鼠伤寒沙门氏菌回复突变试验(Ames试验),小鼠骨髓多染红细胞微核试验,固定剂量蓄积毒性系数法。 结果: 小鼠睾丸M1期精母细胞染色体畸变数阴性对照组与特丁净各剂量组间差异无统计学意义(P>0.05), 而阴性对照组和特丁净各剂量组均低于环磷酰胺组(P<0.05);小鼠骨髓多染红细胞微核率阴性对照组与特丁净原药各剂量组间差异均无统计学意义(P>0.05),而阴性对照组和特丁净各剂量组均明显低于环磷酰胺组(P<0.01);四株试验菌在各试验剂量下(活化或非活化)均没有引起自发回变数呈2倍的增加,5.0 mg/皿剂量组对四个菌株均有抑菌作用,而0.5、1.0、2.0 mg/皿组无剂量反应关系。特丁净原药蓄积系数为1.4。 结论: 特丁净原药根据《农药登记毒理学试验方法》评定标准,未呈现致突变性,小鼠骨髓多染红细胞微核试验在所选剂量范围内结果为阴性,小鼠睾丸精母细胞染色体畸变试验在所选剂量范围内结果为阴性,但蓄积毒性明显。     

胡椒碱的致突变作用

背景与目的： 探讨胡椒碱的致突变性。 材料与方法： 用昆明种小鼠骨髓微核实验、小鼠次级精母细胞染色体畸变实验和精子畸变试验研究胡椒碱的致突变性。 结果： 胡椒碱574 mg/kg、287 mg/kg剂量组的小鼠骨髓微核率及小鼠次级精母细胞畸变率较阴性对照组显著增加(P均<0.01);胡椒碱各剂量组精子畸变率较阴性对照组均显著增加(P均<0.01)。 结论： 在本实验条件下,胡椒碱有致突变的作用。     

乙二醇体内微核试验

本文对乙二醇进行了小鼠骨髓嗜多染红细胞(PCE)微核试验和小鼠胎肝嗜多染红细胞微核试验。2组剂量的乙二醇(40％LD50和80％LD50)均未引起小鼠骨髓PCE微核率的显著改变(P>0.05),阳性对照组与阴性对照组比较有极显著差异(P<0.001),说明乙二醇在小鼠骨髓PCE微核试验中呈阴性结     

红花对小鼠骨髓和人淋巴细胞微核形成的影响

本文采用小鼠骨髓和人淋巴细胞微核试验方法测试了新疆产的红花的诱变性。结果表明,红花水提取物和乙醚提取物均能诱发小鼠骨髓嗜多染红细胞(PCE)微核率升高。红花水提取物的剂量在4～20ml/kg体重范围内,乙醚提取物剂量在1～4ml/kg体重诱发的小鼠骨髓PCE微核率分别为5.16±0.83‰～8.33±0.76‰,3.83±0.48～5.17±0.83‰,与阴性对照(2.5±0.34‰)比较,差异极显著(P<0.01)。红花水提取物亦能诱发人淋巴细胞微核率升高,在实验范围内(0.5～1.5μl/ml)诱发的微核率(3‰～6‰)与阴性对照(2‰)比较有显著性差异(P<0.05)。     

氟化钠诱变性的研究

氟化钠诱变性的研究郭琳，席小平，贾继峰，陈俊文，李建国（太原山西省肿瘤研究所０３００００）为研究无机氟的诱变性，我们采用经口给大、小鼠喂氟化钠，观察其骨髓嗜多染红细胞（ＰＣＥ）的微核率及睾丸初级精母细胞染色体畸变率的方法，进行了研究。①模拟地氟病重病...     

环磷酰胺与异环磷酰胺对小鼠骨髓及胎肝微核率的影响

目的与方法 :本文研究了受孕小鼠尾静脉注射环磷酰胺 (CP)和异环磷酰胺 (IFO)对母鼠骨髓和胎肝微核频率及嗜多染红细胞与正成红细胞比率 (PCE/NCE)的影响。结果 :CP和IFO分别在 5mg/kg .bw时均不诱发母鼠骨髓、胎肝微核率升高和PCE/NCE比率显著变化。当剂量升高至 15mg/kg .bw时 ,CP和IFO诱发骨髓微核率分别为 15 .40± 3.0 5‰和 12 .2 0± 3.5 6‰ ,诱发胎肝微核率分别为 2 3.6 0± 3.6 5‰和 2 1.0 0± 5 .15‰ ,与对照组比较均有显著差别 (P <0 .0 5 )。当剂量为 30mg/kg .bw时 ,微核率升高更显著 ,有明显剂量—效应关系。两药在诱发微核的剂量条件下 ,均可使骨髓和胎肝PCE/NCE比率呈剂量依赖性下降。同等剂量条件下 ,两药对胎肝的作用均明显强于各自对骨髓的作用 ,但IFO对两种组织微核率及PCE/NCE的影响均轻于CP对相应组织的作用。结论 :鉴于CP和IFO都可进入骨髓和透过胎盘屏障引起染色体损伤 ,提示对生产和操作人员应采取必要的防护措施 ;对临床使用的患者要密切监测两者的毒副作用。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.