刺五加对环磷酰胺所致小鼠微核率影响的研究

目的　研究刺五加对环磷酰胺所致小鼠微核率的影响 ,以探讨其对突变的拮抗作用。方法　 6 0只小鼠随机分为 6组 ,连续用刺五加或蒸馏水灌胃 17d ,并在第 13d一次性腹腔注射环磷酰胺 ,之后连续用尾血涂片 5次 ,荧光显微镜观察计数微核 (MN)。结果　①刺五加无增加微核率作用 ;②环磷酰胺致微核率上升作用明显 ;③刺五加可以降低微核发生率 ,随剂量升高作用更加明显。结论　刺五加有比较明显抗突变作用 ,可开发利用到肿瘤治疗和延缓衰老等方面     

特安瑞林(Treplorelin)的致突变与致畸作用的研究

特安瑞林（Ｔｒｅｐｌｏｒｅｌｉｎ）的致突变与致畸作用的研究陆其明（上海医科大学公共卫生学院，２０００３２）特安瑞林（Ｔｒｅｐｌｏｒｅｌｉｎ，Ｄ－Ｔｒｐ－６－ＬＨＲＨ）是一种用于治疗子宫肌瘤的新药，其药理作用能促进性腺激素释放，使子宫内膜脱落和子宫肌瘤...     

Ascorbic acid (vitamin C) modulates the mutagenic effects produced by an alkylating agent in vivo

Recent reports suggest that ascorbic acid (vitamin C) inhibits tumorigenesis as well as exerts a protective effect against mutagenesis in vitro; however, there is no information on its ability to affect gene mutations induced in vivo. In this study, we have investigated the antimutagenic effects of ascorbic acid on the frequency of 6-thioguanine-resistant (6-TGr) T-lymphocytes produced in Fischer 344 rats dosed with the direct-acting alkylating agent, N-ethyl-N-nitrosourea (ENU). The freqeuncy of 6-TG^r T-lymphocytes from the spleen measured five weeks after ENU treatment indicated that ENU produced a substantial mutagenic response. Pretreatment and/or post-treatment of rats with ascorbic acid administered in the drinking water appeared to inhibit the response, but the inhibition was statistically significant only when data from the various dosing schedules were pooled. In addition, there was no clear dose-dependency to the inhibitory effect of ascorbic acid. To further evaluate the time effects of the vitamin supplement on ENU mutagenicity, rats were exposed to the mutagen together with ascorbic acid, which was given continuously for the entire duration of the experiment. At specific times after ENU treatment, the frequency of 6-TG^r T-cells was determined in lymphocytes isolated from the spleen and the thymus. Time-dependent increases in the frequency of 6-TG^r T-cells were observed with ENU treatment; ascorbic acid significantly reduced the ENU-mediated mutagenic responses, most dramatically in the spleen at weeks 6 and 8 (P < 0.0001), and to a lesser extent in the thymus (P < 0.01 at week 6 and P < 0.006 at week 8). Our data suggest that ascorbic acid intake affects the in vivo mutagenicity of ENU, a direct-acting mutagen/carcinogen, and that the reported inhibitory effects of the antioxidant on carcinogenesis may be partially mediated by its effects on mutagenesis. Although it is difficult to extrapolate from rodent studies to humans, the results presented suggest an explanation for epidemiological data that link vitamin C ingestion with decreased cancer risk. © 1994 Wiley-Liss, Inc.     

Mutagenicity,antioxidant potential,and antimutagenic activity against hydrogen peroxide of cashew (Anacardium occidentale) apple juice and cajuina

Fresh and processed cashew (Anacardium occidentale) apple juice (CAJ) are among the most popular drinks in Brazil. Besides their nutritional benefits, these juices have antibacterial and antitumor potential. The chemical constituents of both the fresh juice and the processed juice (cajuina) were analyzed and characterized as complex mixtures containing high concentrations of vitamin C, various carotenoids, phenolic compounds, and metals. In the present study, these beverages exhibited direct and rat liver S9-mediated mutagenicity in the Salmonella/microsome assay with strains TA97a, TA98, and TA100, which detect frameshifts and base pair substitution. No mutagenicity was observed with strain TA102, which detects oxidative and alkylating mutagens and active forms of oxygen. Both CAJ and cajuina showed antioxidant activity as determined by a total radical-trapping potential assay. To test whether this antioxidant potential might result in antimutagenesis, we used a variation of the Salmonella/microsome assay that included pre-, co-, and posttreatment of hydrogen peroxide-exposed Salmonella typhimurium strain TA102 with the juices. CAJ and cajuina protected strain TA102 against mutation by oxidative damage in co- and posttreatments. The antimutagenic effects during cotreatment with hydrogen peroxide may be due to scavenging free radicals and complexing extracellular mutagenic compounds. The protective effects in posttreatment may be due to stimulation of repair and/or reversion of DNA damage. The results indicate that CAJ and cajuina have mutagenic, radical-trapping, antimutagenic, and comutagenic activity and that these properties can be related to the chemical constituents of the juices.     

六种中草药抗突变及抗肿瘤活性的实验报告

目的:探讨仙鹤草、山楂、香菇、杏仁、大枣、板蓝根等6种中草药的抗突变抗肿瘤作用及其机制.方法:采用抗突变和致突变同步快速试验研究了6种中草药的抗突变和致突变性;采用体外抑瘤试验研究了6种中草药的4个浓度组对4种肿瘤细胞的抑制作用.结果:经加和不加大鼠肝脏微粒体酶 (S9) 2种试验,6种中草药均未显示有致突变毒性,香菇、山楂、杏仁、大枣显示对MMC引起的致突变作用有拮抗效应;仙鹤草、山楂、香菇水溶性提取液的各浓度组对4种肿瘤细胞的3H-TdR掺入均有抑制作用,且随浓度的增加,抑制作用有增强趋势.结论:香菇、山楂、杏仁、大枣具有抗突变活性,仙鹤草、山楂、香菇对MT-Ⅱ、L929、SK、K562 4种细胞的DNA合成有明显抑制作用.     

Effects of spermine on formation of HGPRT− mutants induced by ethylmethanesulfonate,methylmethanesulfonate, and mitomycin C in V79 chinese hamster cells

Spermine is a polyamine found in bacteria, animal, and plant tissues. It is involved in a variety of biological processes, and its interaction with DMA stabilizes the secondary structure of the double helix. Spermine is one of the first reported antimutagens, reducing the mutation rate in several prokaryotic test systems, while in eukaryotic organisms conflicting results have been obtained. In light of the significant antimutagenic effect of spermine, it is important to evaluate its activity in mammalian cells in culture. The present study was undertaken to evaluate the ability of spermine to suppress the level of HGPRT mutants induced by ethylmethanesulfonate, methylmethanesulfonate, and mitomycin C. Spermine reduced the mutation frequency induced by ethylmethanesulfonate and methylmethanesulfonate but did not affect survival; with mitomycin C survival was reduced but mutation rate was not influenced.     

MeIQ及煎鱼提取物的致突变作用及抑制物的初步研究

用Ames实验方法检测煎鱼提取物及MelQ,发现它们具有很强的致突变作用。在实验中同时加入新鲜蔬菜,水果提取物及绿茶抗氧化剂T6.能明显抑制它们的致突变作用,其中以绿茶抗氧化剂T6作用最强。提示动物性食品经不适当的加工方式,如高温烹调后,可能会产生致突变、致癌物,而食入新鲜蔬菜、水果、饮绿茶等对肿瘤可能有一定的预防作用。     

Evaluation of the mutagenicity of beta-myrcene in mammalian cells in vitro

The genotoxicity of the terpene beta-myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 micrograms/ml (limit of solubility) in the presence and absence of S9-mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt-locus in V79-cells. Tests with and without S9-mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE-inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79-cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of premutagens and precarcinogenes is discussed.     

The antimutagenic effect of mistletoe lectin (Viscum album L. var. coloratum agglutinin)

A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anticancer activity, was isolated from mistletoe. In this study, we investigated the antimutagenic potentials of VCA by using the pre-incubation method of the Ames test (Salmonella typhimurium TA98 and TA100) in the presence or absence of S9 mixture. Viscum album L. var. coloratum agglutinin was assessed for its antimutagenic properties against the mutagens 2-aminoanthracene (2AA) and furylfuramide (AF-2) for strain TA98, and sodium azide (NaN(3) ) and 2-aminoanthracene (2AA) for strain TA100. The concentrations used for this test compound were 100, 200 and 400 μg per plate. Viscum album L. var. coloratum agglutinin showed moderate, but not negligible, protective effects regarding the antimutagenic properties against the direct-acting mutagens NaN(3) and AF-2. Furthermore, VCA was more effective in preventing the mutagenicity of the indirect-acting mutagen 2-AA (in the presence of S9) when tested with both TA98 and TA100. In conclusion, this report has shown broad ranging antimutagenic effects of VCA to numerous mutagens in TA98 and TA100 Salmonella typhimurium strains. Although the data presented here cannot be applied in vivo, they can support other antimutagenic and anticarcinogenic findings for VCA.     

Variety-based variation in the antimutagenic potential of various vegetables and lack of its correlation with their antioxidant capacity

As mutation causes many life-threatening diseases including cancer, a diet enriched with specific vegetables having potential to reduce mutagenesis possesses immense significance. In this study, 41 commonly used vegetables from diverse botanical taxa were evaluated and compared for their relative antimutagenic potential using standard assays [Escherichia coli RNA polymerase β (rpoB)-based Rif^S → Rif^R assay and Ames test] against known mutagens (UV, gamma radiation, 4-nitroquinoline-N-oxide and ethylmethanesulphonate). Significant differences in antimutagenicity were observed even among the cultivars within the same species, as well as at other phylogenetic levels such as genus or family. The effect of cooking in terms of boiling (aquathermal treatment), on the antimutagenicity of these vegetables, was also investigated. In majority of the cases, aquathermal treatment did not affect the antimutagenic potential. The antimutagenicity of these vegetables was not found to correlate well with their antioxidant properties.