Teratogenesis, carcinogenesis, and mutagenesis最新文献

{"title":"Evaluation of relationship between chromosome 22 and p53 gene alterations and the subtype of meningiomas by the interphase-FISH technique.","authors":"T. Yakut, A. Bekar, M. Doygun, H. Acar, U. Egeli, E. Oğul","doi":"10.1002/TCM.10013","DOIUrl":"https://doi.org/10.1002/TCM.10013","url":null,"abstract":"In this study, we investigated the relationship between genetic alterations such as chromosome 22 aneuploidy and p53 gene deletion, and the pathological types of meningioma of typical and aggressive forms. Thirty-four meningiomas (23 typical and 11 aggressive) were examined by application of fluorescence in situ hybridization (FISH) with chromosome 22 specific alpha satellite probe and a combination of p53 locus specific and chromosome 17 centromere specific alpha satellite probes, to evaluate the chromosome 22 aneuploidy and gain or loss of p53 gene along with chromosome 17. The results showed that, although chromosome 22 aneuploidy was seen in 7 out of 23 typical (30.4%) and 4 out of 11 aggressive meningiomas (36.3%), no p53 deletion was detected in typical meningiomas, and p53 deletion was detected in 3 out of 11 aggressive meningiomas (1 atypical and 2 malignant), which had recurrence. There were no simultaneous occurrences of p53 gene deletions between typical and aggressive meningiomas. The present findings indicate that the loss of chromosome 22 may be involved with tumorogenesis of typical and aggressive meningiomas, while p53 gene deletions may be involved with malignant progression and recurrence in the aggressive meningiomas.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"1 1","pages":"217-25"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91216021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effects of ascorbic acid and folinic acid on chromosome aberrations induced by pyrimethamine in vitro.","authors":"Ciĝdem Egel,&nbsp;Rahmi Bilaloĝlu,&nbsp;Nilüfer Aydemir","doi":"10.1002/tcm.10030","DOIUrl":"https://doi.org/10.1002/tcm.10030","url":null,"abstract":"<p><p>In this study, the anticlastogenic effects of ascorbic acid and the protective effect of folinic acid against the formation of chromosomal aberrations in humans by pyrimethamine were investigated. Pyrimethamine is a folic acid antagonist used for the treatment of malaria and toxoplasmosis. In this study, 18 different healthy people, who do not drink alcohol and are non-smokers, were chosen as an experimental group; 0.025 mg/ml pyrimethamine was given to the lymphocyte culture, which had been prepared with the peripheral blood taken from this group. After that each of the following doses were given to the same culture: 20, 40, and 80 mM of ascorbic acid and 25, 50, and 100 mM of folinic acid. The results of the cytogenetic evaluation showed that the aberrations due to pyrimethamine in the chromosomes were reduced by ascorbic acid and folinic acid significantly, depending on the given dose.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"22 5","pages":"353-62"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tcm.10030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21972531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implantation of MNNG crystals into a Triturus intact limb affects mitotic and labeling indices, regeneration rate, and morphogenesis in the contralateral, regenerating limb.","authors":"T Keramitsoglou,&nbsp;E Grispou,&nbsp;L H Margaritis,&nbsp;S Koussoulakos","doi":"10.1002/tcm.10043","DOIUrl":"https://doi.org/10.1002/tcm.10043","url":null,"abstract":"<p><p>Experimental administration of chemical carcinogens to various mammals is highly effective in inducing malignant tumors. In contrast, treatment of regeneration-competent animals even with much higher doses of the same drugs only exceptionally leads to tumor-like growth. Usually, carcinogenic materials implanted or injected into a regenerating limb of urodele amphibia interfere with the regenerative process and frequently lead a). to growth retardation or arrest of regeneration, b). to development of a great variety of abnormal regenerates, and c). to generation of accessory, limb-like structures. Autonomous or experimental incidence of carcinogenesis is extremely low in animals endowed with strong regenerative capabilities. Of exceptional biological significance is the fact that such induced tumors usually regress spontaneously. This unique property of the regeneration-competent animals to resist carcinogenesis provides opportunities to compare non-cancerous alterations in the differentiated state of adult cells to those occurring in neoplasia. The mode of action of the chemical carcinogens on limb regeneration has not yet been clarified with certainty at the cellular and the molecular level. Several scientists claim that the above-mentioned effects might be attributed to local toxic influences of the drugs; therefore the present study was designed to investigate whether the administration of the carcinogen MNNG can affect cell proliferation, histogenesis, and morphogenesis at a region distant from the site of its implantation, even after a relatively long time period. To this end, 40 animals of the species Triturus cristatus had their right hindlimb surgically removed at the distal zeugopod. Then, a small microcrystal (approximately 5 micro g) of MNNG was inserted under the ventral aspect of the skin of the left tarsus in 20 of these animals (groups T and A; see below). Two months later, nine of the MNNG-treated animals were injected intraperitoneally with tritiated thymidine. After 2 h, six of these animals had their right hindlimb amputated at the distal zeugopod, whereas the rest were left to regenerate. The results were evaluated by camera lucida drawings, clearing in methyl benzoate, classical histology, and autoradiography. It was revealed that administration of MNNG at a somatic region (left hindlimb) reduces DNA synthesis and mitosis at a distant place (right hindlimb) even 2 months after MNNG implantation. Despite this, the rate of limb elongation is not substantially reduced. Classical histology revealed normal tissue structure throughout. All regenerated limbs displayed several teratogenic abnormalities.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"22 6","pages":"473-83"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tcm.10043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22079646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of methionine on selenium embryotoxicity in cultured rat embryos.","authors":"M. Usami, H. Tabata, Y. Ohno","doi":"10.1002/TCM.10025","DOIUrl":"https://doi.org/10.1002/TCM.10025","url":null,"abstract":"Effects of methionine, an essential amino acid, on the embryotoxicity of selenium (Se) were examined using the rat embryo culture. Rat embryos at day 9.5 of gestation were cultured for 48 h in the presence of sodium selenite at 10 and 20 microM or sodium selenate at 30 and 100 microM with or without the addition of 1 mM DL-methionine. Selenite at 20 microM or selenate at 100 microM alone increased the incidence of embryonic malformation and inhibited the embryonic growth. The addition of methionine increased the incidence of embryonic malformation at 10 microM of selenite but decreased the incidence of embryonic malformation at 100 microM of selenate. On the other hand, the addition of methionine partially restored the inhibited embryonic growth at 20 microM of selenite or at 100 microM of selenate. It was considered from these results that the methionine availability in the embryonic environment and the oxidation state of Se are critical in Se embryotoxicity.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"37 1","pages":"301-8"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79385627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antisense inhibition of translation initiation factor 3 reverses its oncogenic potential.","authors":"Yi-Xiong Lei,&nbsp;Pius Joseph,&nbsp;Tong-Man Ong","doi":"10.1002/tcm.10037","DOIUrl":"https://doi.org/10.1002/tcm.10037","url":null,"abstract":"<p><p>Recently we have identified, cloned, and characterized the mouse Translation Initiation Factor 3 (TIF3, GenBank Accession Number AF 271072) as a novel cadmium-responsive proto-oncogene. Presently, additional studies regarding the oncogenic potential of TIF3 have been carried out. Transfection of NIH3T3 cells with the pcDNA3.1 expression vector containing the TIF3 cDNA in the sense (5'-->3') orientation resulted in overexpression of the encoded 36 kDa protein. Transfection-mediated overexpression of TIF3 protein resulted in transformation of the cells as evidenced from the appearance of transformed foci. Cotransfection of the cells with a mixture of plasmid DNA consisting of TIF3 cDNA in the sense and in the antisense orientation resulted in significant inhibition of translation of the TIF3 protein. Antisense (3'-->5') TIF3 mRNA-mediated inhibition of translation of TIF3 protein, furthermore, resulted in inhibition of TIF3-mediated transformation of NIH3T3 cells as evidenced from the decrease in the number of transformed foci. These results further confirm that overexpression of TIF3 is oncogenic and the antisense TIF3 mRNA expression reverses its oncogenic potential.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"22 6","pages":"403-9"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tcm.10037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22079124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.","authors":"L. Ozkan, U. Egeli, B. Tunca, N. Aydemir, G. Cecener, G. Akpinar, E. Ergül, C. Cimen, S. Ozuysal, Sibel Kahraman-Çetintaş, K. Engin, Mansoor M Ahmed","doi":"10.1002/TCM.1034","DOIUrl":"https://doi.org/10.1002/TCM.1034","url":null,"abstract":"In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"1 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75697224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-PK inhibitor wortmannin enhances DNA damage induced by bleomycin in V79 Chinese hamster cells.","authors":"Nuno G Oliveira,&nbsp;Matilde Castro,&nbsp;António S Rodrigues,&nbsp;Octávia M Gil,&nbsp;José M Toscano-Rico,&nbsp;José Rueff","doi":"10.1002/tcm.10029","DOIUrl":"https://doi.org/10.1002/tcm.10029","url":null,"abstract":"<p><p>The fungal metabolite wortmannin (WM) is a potent and irreversible inhibitor of the enzyme DNA-dependent protein kinase (DNA-PK), a nuclear serine-threonine kinase, member of the phosphaditylinositol-3 kinase related kinase family. WM has been used in the last few years as a promising radiosensitizer mainly throughout cell survival experiments. However, few studies have addressed the role of DNA-PK inhibition in the repair of DNA lesions generated by antitumor agents. Bleomycin (BLM) is an antitumor agent used in the treatment of various neoplasia with a unique genotoxicity profile that mimics the ionizing radiation effects. In this study, we evaluated the effect of different concentrations of WM on the DNA damage induced by BLM. The cytokinesis-block micronucleus assay (CBMN) in V79 Chinese hamster cells was used as the end-point. WM significantly increased the frequency of micronucleated cells (%MNBN) by about 2.2-fold, the number of micronuclei per binucleated cell (MN/BN) by about 2.4-fold, and also changed the pattern of the distribution of micronuclei induced by BLM. The frequency of micronucleated cells with 2 MN per cell and with > or = 3 MN per cell increased, whereas the frequency of micronucleated cells with 1 MN per cell decreased. WM was not genotoxic but decreased cell proliferation as assessed by the frequency of binucleated cells. Our results show that WM clearly enhances the efficacy of BLM in terms of DNA damage inflicted and therefore reinforces its use as a chemosensitizer.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"22 5","pages":"343-51"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tcm.10029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21972595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of chlorophyllin on mouse embryonic and fetal development in vivo.","authors":"Ma Carmen García-Rodríguez,&nbsp;Pedro Morales-Ramírez,&nbsp;Mario Altamirano-Lozano","doi":"10.1002/tcm.10042","DOIUrl":"https://doi.org/10.1002/tcm.10042","url":null,"abstract":"<p><p>Chlorophyllin (CHL) has proven that there is antimutagenic and anticarcinogenic activity in several organisms without causing lethal effects. However, there is no information about its effects when it is administered in gestation. In the present study, we assessed possible effects of CHL when it was administered to CD-1 mice on the 8th day of gestation using the same doses and administration route used in ours previous antimutagenic and antigenotoxic studies. Females were exposed to a single dose of CHL by i.p. injection (20, 40, 50, or 100mg/kg b.w.). On day 18 all dams were subjected to cesarean section and the fetuses were examined with common teratological methods. Results show that CHL-treatment induced total litter loss and is dose-dependent, probably due to either the interaction between CHL and some general control mechanisms of embryo development or by an impairment of maternal-fetal interactions. The analysis of uterine horns of the CHL-treated females with total litter loss revealed the presence of green rings in the uterus. Results show the inverse relationship between the number of live implants and the frequency of green rings, indicating implantation sites where embryo death and early resorptions occurred. Although CHL was given in a single dose on day 8 in this study, the results indicate that CHL is associated with significant embryo lethality.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"22 6","pages":"461-71"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tcm.10042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22079645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of modification of rat hepatocarcinogenesis by fernane-type triterpenoids, isolated from a Euphorbia genus.","authors":"R. Karim, S. Iwai, K. Morimura, H. Wanibuchi, R. Tanaka, S. Matsunaga, A. Yoshitake, S. Fukushima","doi":"10.1002/TCM.10024","DOIUrl":"https://doi.org/10.1002/TCM.10024","url":null,"abstract":"Inhibitors of topoisomerases, enzymes that produce an unusual type of DNA damage, are considered as antitumor agents. Recently it has been reported that the fernane-type triterpenoid EC-2 and its hydroxyl derivative, isolated from Euphorbia, are potent topoisomerase II inhibitors. In this study, the modifying effects of EC-2 and EC-4 on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the liver of rats were investigated using a medium-term bioassay system. Fisher 344 male, 6-week-old rats were given a single intraperitoneal injection (200 mg/kg b.w.) of diethylnitrosamine or saline at the beginning of the experiment and subjected to 2/3 partial hepatectomy at the 3rd week. The test compounds were administered five times/week by i.g. gavage at a dose of 1 mg/kg b.w. from 2 to 8 weeks. Quantitation of the numbers and areas per cm(2) of induced GST-P positive foci did not demonstrated any significant differences among the groups and no variation in cell proliferation as indicated by 5-bromo- 2'-deoxyuridine (BrdU) labeling. Our results suggest that EC-2 and EC-4 have no modifying effects on rat hepatocarcinogenesis.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"81 1","pages":"293-9"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85521966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of genetic susceptibility to non-small cell lung cancer by fragile site expression.","authors":"B. Tunca, G. Cecener, C. Gebitekin, U. Egeli, B. Ediz, I. Ercan","doi":"10.1002/TCM.10014","DOIUrl":"https://doi.org/10.1002/TCM.10014","url":null,"abstract":"Fragile sites are non-staining gaps and breaks in specific points of chromosomes that are inducible by various culture conditions. Previous studies have shown that various clastogenic agents increase expression of fragile sites. In this study, the expression of common fragile sites induced by aphidicolin was evaluated on prometaphase chromosomes obtained from peripheral blood lymphocytes. Chromosomal aberrations and fragile site expression of 60 individuals, including 20 patients with non-small cell lung cancer (NSCLC), 20 of their clinically healthy family members, and 20 age-matched normal healthy controls without history of any cancer type were studied. Both the proportion of damaged cells (P < 0.001) and the mean number of gaps and breaks per cell (P < 0.001) were significantly higher in both the patients and relatives' groups when compared with the control group. However, they were insignificant when the patients were compared to their relatives (P > 0.05). We determined four aphidicolin type common fragile sites in our study. These sites in patients with NSCLC and relatives were the following: 1p21, 2q33, 3p14, and 16q23. In these fragile sites, 2q33, 3p14, and 16q23 sites were statistically significant when compared with control group (P < 0.001, P < 0.0005, and P < 0.05, respectively). Consequently, we believe that fragile site studies may be helpful to detection of cancer risk.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"63 1","pages":"205-15"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88429233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}