Teratogenesis, carcinogenesis, and mutagenesis最新文献

{"title":"Characterization of the mutational specificity of DNA cross-linking mutagens by the Lac+ reversion assay with Escherichia coli.","authors":"T. Ohta, S. Ohmae, K. Yamaya, Y. Kanemichi, S. Tokishita, H. Yamagata","doi":"10.1002/TCM.1015","DOIUrl":"https://doi.org/10.1002/TCM.1015","url":null,"abstract":"The mutational specificities of DNA cross-linking compounds such as cisplatin, transplatin, carboplatin, mitomycin C, psoralen, and 8-methoxypsoralen were investigated in lacZ reversion assay systems of Escherichia coli. Tester strains were constructed by introducing the six kinds of F' plasmids (lacI-, lacZ461, and proAB+), each of which carries a different base-substitution mutation within the lacZ gene. Each of the six possible base-substitution mutations was assayed by Lac+ reversion. Cisplatin induced G.C-->A.T transitions and G.C-->T.A transversions, with the former predominating. Transplatin induced A.T-->G.C transitions in addition to G.C-->A.T transitions and G.C-->T.A. Carboplatin weakly induced G.C-->A.T transitions. On the other hand, mitomycin C induced only G.C-->T.A transversions, while psoralen and 8-methoxypsoralen reactivated with near-UV irradiation induced A.T-->G.C transitions preferentially. The Lac(+) reversion system was very convenient for rapidly determining mutational spectra.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"124 1","pages":"275-82"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73518491","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":"Micronucleus incidence and their chromosomal origin related to therapy in acute lymphoblastic leukemia (ALL) patients: detection by micronucleus and FISH techniques.","authors":"H. Acar, U. Çalişkan, S. Demirel, D. Largaespada","doi":"10.1002/TCM.1022","DOIUrl":"https://doi.org/10.1002/TCM.1022","url":null,"abstract":"Micronucleus assay and dual color-fluorescence in situ hybridization (DC-FISH), using centromere-specific and whole chromosome-specific painting probes, are considered a useful screening test to determine the incidence of micronucleus, their origin and contents. The patients with acute lymphoblastic leukemia (ALL), who had undergone chemotherapy, were analysed before and after treatment with vincristine, methotrexate, daunomycin, prednisone, and asparaginase. The incidence of micronuclei after the antileukemic agent treatment was significantly higher than before the treatment. Application of DC-FISH using a combination of whole chromosome-specific painting probes and the same chromosome-specific alpha-satellite centromeric probe showed that there were no significant differences in the micronucleus incidence for any specific chromosome (chromosomes 7, 8, 11, 17, X, and Y). There were no significant differences between the incidence of centromere-positive micronuclei and the incidence of centromere-negative micronucleus. We concluded that antileukemic agents induced the somatic genetic damage but this damage is not related to any specific chromosome studied.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"52 1","pages":"341-7"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84012048","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":"Detection of DNA strand breaks, DNA-protein crosslinks, and telomerase activity in nickel-transformed BALB/c-3T3 cells.","authors":"Y. Lei, J. K. Chen, Z. L. Wu","doi":"10.1002/TCM.1033","DOIUrl":"https://doi.org/10.1002/TCM.1033","url":null,"abstract":"Although nickel compounds are known carcinogens, the underlying carcinogenic mechanisms are not fully understood. The objective of this research was to determine if the genotoxic lesions of DNA strand breaks and DNA-protein crosslinks are present in nickel-transformed BALB/c-3T3 cells, and to further elucidate the potential carcinogenesis of insoluble and soluble nickel compounds through telomerase activity in nickel-transformed BALB/c-3T3 cell lines. DNA strand breaks, DNA-protein crosslinks and telomerase activity were investigated by single cell gel electrophoresis (comet assay), (125)I-postlabelling techniques, and the TRAP-silver staining assay, respectively. Results showed that both DNA strand breaks and DNA-protein crosslinks were present in nickel-transformed BALB/c-3T3 cells. However, the highest levels of DNA strand breaks and DNA-protein crosslinks were found in insoluble crystalline NiS-transformed cells and high levels of DNA strand breaks and DNA-protein crosslinks were also found in the transformed cells induced by two water-soluble NiCl(2) and NiSO(4) at moderate concentrations of cytotoxicity. These data suggest that these two genetic endpoints are useful biomarkers and are associated with cell transformation and carcinogensis of insoluble and soluble nickel compounds. Also, we found that the crystalline NiS- and NiCl(2)-transformed cells possessed a high telomerase activity. A weak telomerase was found in NiSO(4)-transformed cells. The results seem to indicate that in addition to crystalline NiS, some water-soluble nickel compounds such as NiCl(2) are also highly carcinogenic. These results may partly explain the cell transformation and relative carcinogenic potency of insoluble crystalline NiS, soluble NiCl(2), and NiSO(4).","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"100 4 1","pages":"463-71"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87726801","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":"Alternate splicing at the 3'-end of the human pancreatic tumor-associated mucin MUC4 cDNA.","authors":"A Choudhury,&nbsp;N Moniaux,&nbsp;J Ringel,&nbsp;J King,&nbsp;E Moore,&nbsp;J P Aubert,&nbsp;S K Batra","doi":"10.1002/1520-6866(2001)21:1<83::aid-tcm8>3.0.co;2-3","DOIUrl":"https://doi.org/10.1002/1520-6866(2001)21:1<83::aid-tcm8>3.0.co;2-3","url":null,"abstract":"<p><p>MUC4 is a membrane-bound mucin and is considered as the human homologue of the rat sialomucin complex (SMC). The deduced structural organization of the wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large amino mucin type subunit (MUC4alpha) and a transmembrane subunit (MUC4beta). MUC4beta is a membrane-bound growth factor like subunit and contains three EGF-like domains. The MUC4 gene is expressed in several normal tissues like trachea, lung, and testis. It is not expressed in a normal human pancreas; however, its dysregulation results in high levels of expression in pancreatic tumors and tumor cell lines. Recently, we have demonstrated the presence of alternative splice events in the 3'-end of the MUC4 cDNA that generated new putative variants (sv1-sv10) in normal human testis and in a pancreatic tumor cell line (HPAF). In search of MUC4 variant(s) that are specific to pancreatic adenocarcinoma, we investigated the splicing phenomena in the MUC4 cDNA sequence by using a large panel of pancreatic tumor cell lines. We have identified ten alternative splice events located downstream to the central large tandem repeat domain. These splice events generated 12 variant species (sv4, sv9, sv10-18, and sv21) of MUC4 cDNAs. The deduced amino acid sequence of these variant MUC4 cDNAs revealed two distinct types: a family of secreted and a membrane-associated variant form. Among the members of MUC4 secreted variant family, three (sv4, sv12, and sv13) of ten showed a short 144 residue COOH-terminus compared to 1154 residues in WT-MUC4. The variants with this short COOH-terminus (144 residues) was found in 37% (4/11) of the tumor lines. The putative membrane-bound variant sv10 was detected in 37% (4/11) pancreatic tumor cell lines but not in any normal human tissues. In conclusion, we have identified novel splice variant(s) of MUC4 in pancreatic adenocarcinoma.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"21 1","pages":"83-96"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1520-6866(2001)21:1<83::aid-tcm8>3.0.co;2-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21957820","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":"Antibody constructs for radioimmunodiagnosis and treatment of human pancreatic cancer.","authors":"A Goel,&nbsp;S K Batra","doi":"10.1002/1520-6866(2001)21:1<45::aid-tcm5>3.0.co;2-a","DOIUrl":"https://doi.org/10.1002/1520-6866(2001)21:1<45::aid-tcm5>3.0.co;2-a","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a common disease that is seldom cured. Current approaches to the treatment of PC are not effective because the non-specific nature of both chemotherapy and external beam radiation results in toxicity to normal tissue. Monoclonal antibodies (MAbs) can be used as selective carriers for delivering radionuclides, toxins, or cytotoxic drugs to malignant cell populations. Therefore, MAb-technology has led to a significant amount of research in targeted therapy. Targeted therapy would generally allow the concentration of cytotoxic agents in tumors and would markedly lessen the toxicity to normal tissues, which limits the dosage and effectiveness of systemically administered drugs. A variety of MAbs are being pre-clinically evaluated for the diagnosis and treatment of PC. Novel recombinant antibody constructs hold a promising future in both the diagnosis and treatment of cancer. By genetic-engineering methods, several high affinity antibody fragments with optimum tumor targeting properties, such as higher functional affinity (divalent and multivalent scFvs) and blood residence time (good tumor localization with high radiolocalization index), have been generated. Animal models have permitted the in vivo assessment of these antibody-based reagents, therapeutic/diagnostic radionuclide, radiolabeling conditions, and efficacy of administration regimes. For PC, immunoscintigraphy using MAbs has taken new strides. The use of MAbs and their fragments for radioimmunoguided surgery and therapy of PC has shown encouraging results at preclinical levels and warrants further attention.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"21 1","pages":"45-57"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1520-6866(2001)21:1<45::aid-tcm5>3.0.co;2-a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21957817","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":"Early changes in islet hormone secretion in the hamster pancreatic cancer model.","authors":"J Permert,&nbsp;M Herrington,&nbsp;K Kazakoff,&nbsp;P M Pour,&nbsp;T E Adrian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The diabetic state that is seen at a high frequency in association with pancreatic cancer is characterized by elevated plasma levels of several islet hormones and by marked insulin resistance. Both the diabetic state and insulin sensitivity improve after tumor removal by sub-total pancreatectomy. Impaired glucose tolerance has also been found in the hamster pancreatic cancer model, but conflicting data regarding islet function have been reported. In order to further investigate islet function and secretion during early development of pancreatic cancer, we measured the concentrations of insulin, glucagon, somatostatin, and islet amyloid polypeptide (IAPP) in plasma, pancreatic tissue, and secretin-stimulated pancreatic juice at 12 and 27 weeks after the ductal-cell-specific carcinogen, BOP had been used to induce tumors in Syrian golden hamsters. At 12 weeks after BOP, plasma glucagon levels were significantly increased. An exaggerated plasma-glucose response and concomitant hyperinsulinemia were observed at 27 but not 12 weeks after BOP. Plasma IAPP concentrations, but not glucagon or somatostatin, were elevated at 27 weeks. Tissue concentrations of IAPP were substantially reduced in BOP-treated hamsters at 27 weeks. No differences in hormone concentrations were seen in pancreatic juice from the two groups at either of the two time points investigated. The study showed that islet hormone changes accompany the early development of pancreatic tumors in the hamster pancreatic model. The hormone changes and apparent insulin resistance resemble the metabolic changes found in humans with pancreatic cancer.</p>","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"21 1","pages":"59-67"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21957818","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":"Introduction.","authors":"P M Pour","doi":"10.1002/1520-6866(2001)21:1<3::aid-tcm2>3.0.co;2-p","DOIUrl":"https://doi.org/10.1002/1520-6866(2001)21:1<3::aid-tcm2>3.0.co;2-p","url":null,"abstract":"","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"21 1","pages":"3-5"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1520-6866(2001)21:1<3::aid-tcm2>3.0.co;2-p","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21958558","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":"I. The modulatory effect in genotoxic responses due to age and duration of PHT-therapy in epileptic patients.","authors":"A. Kaul, N. Kalla, S. Goyle","doi":"10.1002/1520-6866(2001)21:2<135::AID-TCM3>3.0.CO;2-7","DOIUrl":"https://doi.org/10.1002/1520-6866(2001)21:2<135::AID-TCM3>3.0.CO;2-7","url":null,"abstract":"Sister chromatid exchange (SCE) frequency has been studied from the peripheral blood lymphocyte cultures of 42 epileptic patients on the anticonvulsant drug phenytoin (PHT) for 3 months and their follow-up (6 and 9 months), of 33 epileptics who had not started therapy (PHT-untreated), and of 40 normal healthy controls, all in the same age group, i.e., 10-30 years. PHT-treated epileptic patients at all three durations of therapy (3, 6, and 9 months) showed higher SCE frequency (P < 0.001) than healthy controls and PHT-untreated patients. There was no significant difference in SCE frequency between control and PHT-untreated patients, suggesting that disease is not associated with an increased frequency of SCEs. The frequency of SCEs seems to be influenced by an age factor, when older treated patients (21-30 years) showed higher SCE frequencies at 3 and 6 months (P < 0.001) and 9 months (P < 0.05) than the younger age group (10-20 years). SCE frequency increased linearly with the duration of therapy, i.e., from 3 months to 9 months. No correlation was found between SCE frequency and sex with respect to controls, PHT-untreated, and PHT-treated subjects. In conclusion, the modulating effect on SCE frequencies elicited by age and duration of therapy has been clearly demonstrated by SCE mean analysis. Teratogenesis Carcinog. Mutagen. 21:135-149, 2001.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"20 1","pages":"135-49"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76807439","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":"Aneuploidy induced in lymphocytes of parents of trisomic 21 children.","authors":"H. Caria, T. Chaveca, J. Rueff","doi":"10.1002/TCM.1025","DOIUrl":"https://doi.org/10.1002/TCM.1025","url":null,"abstract":"A possible predisposition to aneuploidy in trisomic 21 individuals, their parents, and a control group was evaluated. Peripheral blood lymphocytes from those three groups were used to study the induction of micronuclei (MN) by mitomycin C, cyclophosphamide, and quercetin. Induced MN were further analysed by C-banding and CREST antibody. Trisomic 21 individuals have spontaneous frequencies of MN significantly higher than their parents and the control group. Quercetin without metabolic activation induces MN in trisomic 21 and their parents at a significantly higher level than in control group. The group of the parents of trisomic 21 individuals exhibits higher frequencies of induced MN by mitomycin C and cyclophosphamide than controls. Mitomycin C significantly induced CREST-positive-MN in ten of the sixteen parents evaluated. The results obtained seem to suggest a unique behaviour for the parents of trisomic 21 patients consisting in an increased susceptibility to chromosome loss in the presence of clastogenic genotoxicants, suggesting a higher predisposition to aneuploidy.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"68 1","pages":"369-82"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75635694","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":"Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice.","authors":"Y. Nakanishi, F. Bai, Koji Inoue, K. Takayama, X. Pei, T. Harada, M. Izumi, K. Kimotsuki, H. Tokiwa, Nobuyuki Hara","doi":"10.1002/TCM.1027","DOIUrl":"https://doi.org/10.1002/TCM.1027","url":null,"abstract":"Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated \"Yusho,\" the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on 1-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.","PeriodicalId":22336,"journal":{"name":"Teratogenesis, carcinogenesis, and mutagenesis","volume":"52 1","pages":"395-403"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82208304","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}