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Indian medicinal plants as a reservoir of protective phytochemicals. 作为保护性植物化学物质储存库的印度药用植物。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10055
Saroj Arora, Kamaljit Kaur, Swayamjot Kaur

India is one of the 12 mega diversity countries in the world so it has a vital stake in conservation and sustainable utilization of its biodiversity resources. Plant secondary metabolites have been of interest to man for a long time due to their pharmacological relevance. With this in view, the bark powder of Acacia auriculiformis, A. nilotica, Juglans regia, and the fruit powder of Terminalia bellerica, T. chebula, Emblica officinalis, and a combination drug "Triphala," which are known to be rich in polyphenols, were tested for their antimutagenic activities. Antimutagenic activities of the extracts were estimated by employing the plate incorporation Ames Salmonella histidine reversion assay by using the frame shift mutagen tester strain TA98 and base pair substitution strain TA100 against direct acting mutagens (NPD, sodium azide), and the S9-dependent mutagen 2-aminofluorene(2AF). Acetone extracts of all the plants exhibited significant antimutagenic activities among the other extracts tested, but an acetone extract of Acacia nilotica showed a marked anti-mutagent effect. Furthermore, it was more effective against indirect acting mutagen, 2AF, in both TA98 and TA100 tester strains of Salmonella typhimurium than against the direct acting mutagens. The results indicate that an acetone extract of bark and fruit of the medicinal plants under study harbors constituents with promising antimutagenic/anticarcinogenic potential that could be investigated further.

印度是世界上12个生物多样性大国之一,因此保护和可持续利用其生物多样性资源对印度至关重要。植物次生代谢物由于其药理意义,长期以来一直受到人们的关注。有鉴于此,我们测试了金合欢、nilotica、核桃的树皮粉,以及已知富含多酚的Terminalia bellerica、T. chebula、Emblica officinalis的果实粉和一种复方药物“Triphala”的抗诱变活性。采用框架移位诱变试验菌株TA98和碱基对置换菌株TA100对直接作用诱变剂(NPD、叠氮化钠)和s9依赖性诱变剂2-氨基芴(2AF)的抗诱变活性进行平板掺入Ames沙门氏菌组氨酸还原试验。所有植物的丙酮提取物均表现出显著的抗诱变活性,但阿拉伯相思的丙酮提取物表现出显著的抗诱变作用。此外,该制剂对TA98和TA100鼠伤寒沙门菌间接作用诱变剂2AF的抑制效果均优于直接作用诱变剂。结果表明,所研究的药用植物树皮和果实的丙酮提取物中含有具有抗诱变/抗癌潜力的成分,值得进一步研究。
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引用次数: 129
Tumor promotion by metanil yellow and malachite green during rat hepatocarcinogenesis is associated with dysregulated expression of cell cycle regulatory proteins. 甲氨酰黄和孔雀石绿在大鼠肝癌发生过程中的促瘤作用与细胞周期调节蛋白的表达失调有关。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10056
Sanjay Gupta, Monisha Sundarrajan, K V K Rao

Metanil yellow (MY) and malachite green (MG) are textile dyes, which, despite a ban, are used as food-coloring agents. MY and MG have promoter effects on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine (DEN). Tumor-promoting agents are not mutagenic but may alter the expression of genes whose products are associated with hyper-proliferation, tissue remodeling, and inflammation. Cell cycle controls normally function to ensure the integrity of the genome and arrest of cells at G1/S or G2/M checkpoints until all the prerequisite events are completed. In order to understand the mechanism(s) of tumor promotion by MY and MG, we have studied the levels of PCNA, a marker of cell proliferation and cell cycle regulatory proteins, cyclin D1, and its associated kinase, cdk4, cyclin B1, and associated kinase, cdc2. Immunohistochemical staining showed an elevated level of PCNA in animals administered MY and MG subsequent to DEN treatment. Western and Northern blot hybridization showed an increased expression of both cyclin D1 and its associated kinase cdk4, and cyclin B1 and its associated kinase cdc2, in livers of rats administered MY and MG after administration of DEN as compared to untreated or DEN controls. The increased level of mRNA was due to the increased rate of transcription of these genes as studied by run-on transcription assay. These data obtained by the in vivo model of liver tumor development provide strong evidence for a link between dysregulation of the two critical checkpoints of the cell cycle as one of the possible mechanism(s) during tumor promotion by malachite green and metanil yellow.

金属黄(MY)和孔雀石绿(MG)是纺织染料,尽管有禁令,但它们仍被用作食品着色剂。MY和MG对n -亚硝基二乙胺(DEN)诱导的肝脏肿瘤前病变有促进作用。促肿瘤药物不具有诱变性,但可能改变其产物与过度增殖、组织重塑和炎症相关的基因的表达。细胞周期控制通常的功能是确保基因组的完整性,并在G1/S或G2/M检查点阻止细胞,直到所有先决条件事件完成。为了了解MY和MG促进肿瘤的机制,我们研究了细胞增殖和细胞周期调节蛋白cyclin D1及其相关激酶cdk4、cyclin B1和相关激酶cdc2的水平。免疫组织化学染色显示,DEN治疗后给予MY和MG的动物的PCNA水平升高。Western和Northern杂交显示,与未治疗或DEN对照组相比,在给予DEN后给予MY和MG的大鼠肝脏中,细胞周期蛋白D1及其相关激酶cdk4和细胞周期蛋白B1及其相关激酶cdc2的表达均有所增加。mRNA水平的增加是由于这些基因的转录速率增加,这是通过运行转录试验研究的。通过肝脏肿瘤发展的体内模型获得的这些数据提供了强有力的证据,证明细胞周期两个关键检查点的失调与孔雀石绿和金属黄促进肿瘤的可能机制之一有关。
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引用次数: 67
Ascorbic acid potentiates mitomycin C-induced micronuclei and sister chromatid exchanges in human peripheral blood lymphocytes in vitro. 抗坏血酸增强丝裂霉素c诱导的体外人外周血淋巴细胞微核和姐妹染色单体交换。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10064
A P Krishnaja, N K Sharma

Vitamin C (l-ascorbic acid), an effective free radical scavenger present as ascorbate in most biological systems, is one of the most extensively studied antioxidant vitamins. Vitamin C acts as either a free radical scavenger or a pro-oxidant producing hydrogen peroxide and free radicals. The modulatory effect of L-ascorbic acid (AA) on Mitomycin C (MMC) induced chromosome damage has been evaluated in human peripheral blood lymphocytes in vitro. The effect of L-ascorbic acid, 200 microg/ml as 1- and 2-h pretreatment on the frequencies of the biomarkers micronuclei (MN), sister chromatid exchanges (SCEs), and chromosome aberrations (CA) induced by mitomycin C 0.1 and 0.2 microg/ml has been studied. AA pretreatment caused a statistically significant increase in MMC-induced MN and SCE frequencies for all treatment groups, but did not show an increase in induced chromosome aberrations compared to MMC treatment alone. Cell division delays caused by MMC was reversed in the presence of AA. Interindividual variability in MMC as well as AA plus MMC-induced MN, SCE, and CA frequencies were evident. Ascorbic acid potentiated MMC-induced chromosome damage in human lymphocytes in vitro. The potentiation observed has to be viewed in the light of metal ion catalysed autooxidation of AA in oxygenated media and the existence of an antioxidant system in vivo that inactivates oxyradicals before their interaction with DNA.

维生素C (l-抗坏血酸)是一种有效的自由基清除剂,作为抗坏血酸存在于大多数生物系统中,是研究最广泛的抗氧化维生素之一。维生素C可以作为自由基清除剂或促氧化剂产生过氧化氢和自由基。在体外研究了l -抗坏血酸(AA)对丝裂霉素C (MMC)诱导的人外周血淋巴细胞染色体损伤的调节作用。研究了200 μ g/ml l -抗坏血酸预处理1 h和2 h对丝裂霉素c0.1和0.2 μ g/ml诱导的生物标志物微核(MN)、姐妹染色单体交换(SCEs)和染色体畸变(CA)频率的影响。AA预处理导致所有治疗组MMC诱导的MN和SCE频率有统计学意义的增加,但与单独MMC治疗相比,未显示诱导的染色体畸变增加。在AA存在的情况下,MMC引起的细胞分裂延迟被逆转。MMC以及AA + MMC诱导的MN、SCE和CA频率的个体间差异是明显的。抗坏血酸增强mmc诱导的体外人淋巴细胞染色体损伤。观察到的增强作用必须从金属离子催化氧化介质中AA的自氧化和体内存在的抗氧化系统的角度来看待,该系统在自由基与DNA相互作用之前灭活了自由基。
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引用次数: 23
Developmental toxicity evaluation of the new fluoroquinolone antibacterial DW-116 in rats. 新型氟喹诺酮类抗菌药物DW-116对大鼠发育毒性评价。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10066
Jong-Choon Kim, Dong-Ho Shin, Sung-Ho Kim, Tae-Ho Ahn, Seong-Soo Kang, Beom-Su Jang, Choong-Yong Kim, Moon-Koo Chung

We have recently reported that the fluoroquinolone antibacterial DW-116 induces a significant developmental toxicity in rat. The present study was conducted to better understand the teratogenic effects of DW-116 at several developmental toxic doses in rats. DW-116 was orally administered to pregnant rats from gestational day (GD) 6 through 16 at dose levels of 0, 320, 400, and 500 mg/kg/day. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. At above 400 mg/kg, severe decreases in maternal body weight gain, food consumption, litter size, fetal weight and placental weight, and severe increases in resorption rate and fetal morphological alterations were observed. At 320 mg/kg, mild decreases in maternal body weight gain, food consumption, fetal weight and placental weight, and mild increases in fetal variations and retardations were observed. These results suggest that DW-116 is embryotoxic at above 320 mg/kg/day and is embryolethal and teratogenic at above 400 mg/kg in pregnant rats and that DW-116 is a selective developmental toxicant in rat conceptuses.

我们最近报道了氟喹诺酮类抗菌药物DW-116对大鼠具有显著的发育毒性。本研究旨在更好地了解DW-116在不同发育毒性剂量下对大鼠的致畸作用。DW-116分别以0、320、400和500 mg/kg/天的剂量给药于妊娠第6至16天妊娠大鼠。所有孕妇在妊娠第20天进行剖宫产,检查胎儿的外部、内脏和骨骼异常。当剂量超过400 mg/kg时,母体增重、食量、产仔数、胎儿体重和胎盘重量均显著降低,吸收率显著升高,胎儿形态发生改变。在320 mg/kg剂量下,产妇体重增加、食物消耗、胎儿体重和胎盘体重轻度下降,胎儿变异和发育迟缓轻度增加。以上结果表明,DW-116在320 mg/kg/d以上对妊娠大鼠具有胚胎毒性,在400 mg/kg以上对妊娠大鼠具有胚胎致毒和致畸作用,DW-116是大鼠妊娠期的选择性发育毒物。
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引用次数: 8
Antigenotoxic potential of certain dietary constituents. 某些膳食成分的抗基因毒性潜力。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10059
Yogeshwer Shukla, Annu Arora, Pankaj Taneja

The human diet contains a variety of compounds that exhibit chemopreventive effects towards an array of xenobiotics. In the present study, the antigenotoxic potential of selected dietary constituents including Diallyl sulfide (DAS), Indole-3-carbinol (I3C), Curcumin (CUR), and Black tea polyphenols (BTP) has been evaluated in the Salmonella typhimurium reverse mutation and mammalian in vivo cytogenetic assays. In addition, the anticlastogenic effect of the above dietary constituents was identified towards Benzo(a)pyrene (BaP) and cyclophosphamide- (CP) induced cytogenetic damage in mouse bone marrow cells. The induction of BaP and CP induced chromosomal aberrations, micronuclei formation, and sister chromatid exchanges (SCEs) were found to be inhibited in a dose-dependent manner by DAS, I3C, CUR, and BTP. Thus the study reveals the antimutagenic potential of these dietary compounds towards BaP- and CP-induced genotoxicity in microbial and mammalian test systems.

人类饮食中含有多种化合物,这些化合物对一系列外源性物质具有化学预防作用。本研究通过鼠伤寒沙门氏菌反向突变和哺乳动物体内细胞遗传学试验,对膳食成分二烯丙基硫醚(DAS)、吲哚-3-甲醇(I3C)、姜黄素(CUR)和红茶多酚(BTP)的抗毒素潜力进行了评价。此外,还研究了上述膳食成分对苯并(a)芘(BaP)和环磷酰胺- (CP)诱导的小鼠骨髓细胞遗传损伤的抗裂作用。发现DAS、I3C、CUR和BTP以剂量依赖的方式抑制BaP和CP诱导的染色体畸变、微核形成和姐妹染色单体交换(sce)。因此,该研究揭示了这些膳食化合物在微生物和哺乳动物试验系统中对BaP和cp诱导的遗传毒性的抗诱变潜力。
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引用次数: 48
X chromosomal abnormalities in Indian adolescent girls. 印度少女的X染色体异常。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10052
Bani Bandana Ganguly, Sumedha Sahni

In girls of adolescent age, primary amenorrhea is a major problem and it is often suspected as Turner syndrome (TS), with complete or partial absence of one of the two X chromosomes. The girls who are unable to menstruate are primarily investigated by the gynecologists with the help of a physical examination, sonogram of the pelvis, endocrinologic tests, and ultimately cytogenetic analysis. Chromosomal analyses have been carried out in 280 such cases that were referred from different parts of the country. The standard protocol for peripheral blood lymphocyte culture was followed for metaphase chromosome preparation and conventional analysis of G-banded chromosomes. A total of 29% cases were found to have some chromosomal abnormality, including TS and testicular feminization syndrome involving sex chromosomes. Amongst those with sex chromosomal anomaly, 34% had evidence of a 46,XY karyotype in phenotypic females and 51% had pure line 45,X or mosaic with normal XX or other aberrations in X. The classification of the TS group further showed the spectrum of variant TS in Indian adolescent girls who suffered from absence or delayed menarche to correspond well with the Belgian, Danish, or Russian population. However, it has been reported that only 1% of the pure line 45,X conception is viable, indicating the necessity of mosaicism with X or Y chromosome. It has been understood that conventional banding analysis is absolutely necessary for segregating the variant nature of TS. In addition, molecular genetic or molecular cytogenetic investigations can determine the nature of mosaicism. The present study further indicated the involvement of autosomes in causing improper sexual development in girls of adolescent age.

在青春期的女孩中,原发性闭经是一个主要问题,通常被怀疑为特纳综合征(TS),两条X染色体中的一条完全或部分缺失。不能来月经的女孩主要由妇科医生在体格检查、骨盆超声检查、内分泌检查和细胞遗传学分析的帮助下进行调查。对来自全国不同地区的280例此类病例进行了染色体分析。采用外周血淋巴细胞培养标准方案进行中期染色体制备和g带染色体常规分析。共有29%的病例发现染色体异常,包括涉及性染色体的TS和睾丸女性化综合征。在性染色体异常的人群中,34%的表型女性有46、XY核型,51%的人有45、X系或嵌合系,X系有正常的XX或其他畸变。TS组的分类进一步表明,出现月经初潮缺席或延迟的印度少女的变异TS谱与比利时、丹麦或俄罗斯人群相符。然而,据报道,只有1%的纯45系,X受孕是可行的,这表明与X或Y染色体嵌合的必要性。传统的条带分析对于分离TS的变异性质是绝对必要的,此外,分子遗传学或分子细胞遗传学研究可以确定嵌合的性质。本研究进一步表明常染色体参与导致青春期女孩性发育不正常。
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引用次数: 10
Customized cDNA microarray for expression profiling of environmentally important genes of Pseudomonas stutzeri strain KC. 定制cDNA微阵列对stutzeri假单胞菌菌株KC环境重要基因的表达谱分析。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10054
Javed Musarrat, Syed A Hashsham

DNA microarray is a powerful tool for parallel detection of multiple target genes in biological systems. In this study, a low-density DNA microarray has been custom designed by using Pseudomonas stutzeri strain KC ORFs that are implicated in carbon tetrachloride degradation. PCR amplified strain KC probes of varying lengths were obtained using ORF-specific primers. Purified short probes (80-120 bp) and full-length amplicons were directly immobilized on gamma-aminosilane coated and superaldehyde trade mark glass substrates without any chemical modification. The full-length amplicons exhibited a much higher signal compared to the shorter probes upon hybridization with the Cy5/Cy3-labeled unfragmented cDNA targets. The meager signal with the shorter probes limits the advantage of using the multiple probes of the same genes for enhancing the specificity of hybridization with environmental samples. Nevertheless, expression analysis of strain KC genome, under controlled laboratory conditions, revealed the constitutive expression of at least 11 putative ORFs of the pdt operon. Comparatively weaker hybridization signals with the cDNA from mutant cells suggested a low abundance of mRNA transcripts in the KC 1896 mutant. Similar expression levels of the pdt ORFs I, J, K, M, N, O, P, and fur gene both under iron-limiting conditions and in presence of iron (20 micro M Fe(3+)) suggested metal ion-independent regulation of the pdt operon. The tailor-made array with strain KC gene-specific probes served as a model for demonstrating the utility of cDNA microarray technology in monitoring the expression of environmentally important genes in bacteria.

DNA芯片是生物系统中多目标基因并行检测的有力工具。在这项研究中,利用与四氯化碳降解有关的斯图氏假单胞菌菌株KC orf定制了一种低密度DNA微阵列。利用orf特异性引物获得不同长度的PCR扩增菌株KC探针。纯化的短探针(80- 120bp)和全长扩增子直接固定在γ -氨基硅烷涂层和超醛商标玻璃衬底上,不进行任何化学修饰。与短探针相比,全长扩增子与Cy5/ cy3标记的未片段cDNA靶标杂交时表现出更高的信号。较短探针的微弱信号限制了使用相同基因的多个探针来增强与环境样品杂交的特异性的优势。然而,在受控的实验室条件下,菌株KC基因组的表达分析揭示了pdt操纵子至少11个假定的orf的组成性表达。与突变细胞的cDNA杂交信号相对较弱,表明KC 1896突变体的mRNA转录物丰度较低。在限铁条件下和铁(20 μ M Fe(3+))存在下,pdt ORFs I、J、K、M、N、O、P和fur基因的表达水平相似,表明pdt操纵子的调控不依赖于金属离子。特制的菌株KC基因特异性探针阵列作为模型,展示了cDNA微阵列技术在监测细菌中环境重要基因表达方面的实用性。
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引用次数: 10
A quantitative structure-activity relationship (QSAR) study of mutagenicity in several series of organic chemicals likely to be activated by cytochrome P450 enzymes. 几种可能被细胞色素P450酶激活的有机化学物质致突变性的定量构效关系(QSAR)研究。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10073
David F V Lewis, Costas Ioannides, Dennis V Parke

The results of quantitative structure-activity relationship (QSAR) studies on six series of compounds exhibiting indirect mutagenic activity are reported. These findings demonstrate the importance of frontier orbital energies and, in some cases, frontier orbital electronic populations to overall mutagenicity in diverse polyaromatic hydrocarbons, benzidines and aminobiphenyls, benzonitrofurans, nitrogenous cooked-food mutagens, benzanthracenes, and chrysenes. The correlations between structural parameters and mutagenic potency vary from R=0.81 to R=0.97, and these findings are discussed in the context of possible molecular mechanisms of mutagenicity. In particular, it is generally regarded that cytochrome P450-mediated activation of polyaromatic hydrocarbons and their amino derivatives plays an important role in mutagenic activity. In this respect, it is apparent that enzymes of the cytochrome P4501 (CYP1) family are closely associated with the metabolic activation of polyaromatic mutagens and carcinogens via the generation of reactive intermediates (usually electrophilic in nature) that attack DNA. The findings presented in this study indicate that QSAR analyses on several series of compounds are consistent with the known evidence of procarcinogen activation mechanisms, particularly for polyaromatic hydrocarbons and their heterocyclic/amino derivatives, pointing to the importance of frontier orbital energy values in particular.

本文报道了6个具有间接致突变活性的化合物系列的定量构效关系(QSAR)研究结果。这些发现证明了前沿轨道能量的重要性,在某些情况下,前沿轨道电子居群对各种多芳烃、联苯胺和氨基联苯、苯并硝基呋喃、含氮熟食诱变剂、苯并蒽和蒽的总体诱变性。结构参数与诱变效力之间的相关性在R=0.81 ~ R=0.97之间,这些发现在可能的致突变性分子机制的背景下进行了讨论。特别是,一般认为细胞色素p450介导的多芳烃及其氨基衍生物的活化在致突变活性中起着重要作用。在这方面,很明显,细胞色素P4501 (CYP1)家族的酶通过产生攻击DNA的活性中间体(通常是亲电的)与多芳诱变剂和致癌物的代谢激活密切相关。本研究的结果表明,对几个系列化合物的QSAR分析与已知的致癌原激活机制的证据是一致的,特别是对多芳烃及其杂环/氨基衍生物,特别指出前沿轨道能值的重要性。
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引用次数: 10
Inhibitory effect of local ischaemic preconditioning in total body irradiated rats. 全身辐照大鼠局部缺血预处理的抑制作用。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10074
Piotr Walichiewicz, Waldemar M Przybyszewski, Jerzy Jochem, Maria Widel, Aleksandra Koterbicka, Miroslaw Snietura

The aim of this study was to explore the relationship between local ischaemic preconditioning and the effectiveness of fractionated radiotherapy. The rat serum, bone marrow, and small intestine were examined for oxidative changes induced by total body irradiation with gamma rays with applied local ischaemic preconditioning immediately before irradiation. Serum concentrations of TBA-RS examined 12 hours after the last irradiation did not reveal any differences among the groups of animals analyzed. Twenty-four hours after the last dose of irradiation, the serum concentrations of TBA-RS varied in particular groups (P<0.0001). The concentration of triglycerides in the serum of local preconditioned ischaemia and irradiated animals showed a reversed shape similar to the TBA-RS fluctuation (P<0.003). The level of uric acid in the serum of animals treated only with radiation is slightly higher than the level of this acid in the serum of the local preconditioned ischaemia radiation group (P<0.58). The number of bone marrow polychromatic erythrocytes did not appear to differ substantially in both irradiated groups. At the first 12 hours after irradiation, the frequency of micronucleated polychromatic erythrocytes is significantly different in the bone marrow of both groups either in combination with ischaemic preconditioned radiation or with radiation alone (P<0.0002). In irradiated animals without ischaemic preconditioning, on the 3rd day after irradiation the number of crypts increased and in the next days decreased achieving the level of the control group on the 7th day. Irradiated rats with local ischaemic preconditioning did not reveal an increase in the number of crypts. The difference was statistically significant (P<0.05). These data indicate that the local ischaemic preconditioning modifies the radiation peroxidising effects through inhibition of free radical-dependent lipid peroxidation and, probably, other unrecognized mechanisms.

本研究旨在探讨局部缺血预处理与分步放疗效果之间的关系。采用局部缺血预处理的方法,观察γ射线全身照射后大鼠血清、骨髓和小肠的氧化变化。最后一次辐照后12小时检测的血清TBA-RS浓度在各组动物之间没有发现任何差异。最后一次给药24小时后,不同剂量组大鼠血清TBA-RS浓度差异显著(P
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引用次数: 4
Proceedings of the XXVII Annual Conference of the Environmental Mutagen Society of India (EMSI) Symposium on Environmental Genomics and Health Sciences. March 19-21, 2002, Lucknow, India. 印度环境诱变剂学会(EMSI)环境基因组学和健康科学研讨会第二十七届年会论文集。2002年3月19日至21日,印度勒克瑙。
Pub Date : 2003-01-01 DOI: 10.1002/tcm.10048
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引用次数: 0
期刊
Teratogenesis, carcinogenesis, and mutagenesis
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