Princess Takamatsu symposia最新文献

{"title":"Influence of inhibitors of poly(ADP-ribose) polymerase on DNA repair, chromosomal alterations, and mutations.","authors":"Natarajan At, van Zeeland Aa, Zwanenburg Ts","doi":"10.1201/9781003079491-25","DOIUrl":"https://doi.org/10.1201/9781003079491-25","url":null,"abstract":"The influence of inhibitors of poly(ADP-ribose) polymerase such as 3-aminobenzamide (3AB) and benzamide (B) on the spontaneously occurring as well as mutagen induced chromosomal aberrations, sister chromatid exchanges (SCEs) and point mutations has been studied. In addition, we have measured the influence of 3AB on DNA repair following treatment with physical and chemical mutagens. Post treatment of X-irradiated mammalian cells with 3AB increases the frequencies of induced chromosomal aberrations by a factor of 2 to 3. Both acentric fragments and exchanges increase indicating that the presence of 3AB slows down the repair of DNA strand breaks (probably DNA double strand breaks), thus making breaks available for interaction with each other to give rise to exchanges. 3AB, when present in the medium containing bromodeoxyuridine(BrdUrd) during two cell cycles, increases the frequencies of SCEs in Chinese hamster ovary cells (CHO) in a concentration dependent manner leading to about a 10-fold increase at 10 mM concentration. Most 3AB induced SCEs occur during the second cell cycle, in which DNA containing bromouridine (BU) is used as template for replication. BU containing DNA appears to be prone to errors during replication. The extent of increase in the frequencies of SCEs by 3AB is correlated with the amount of BU incorporated in the DNA of the cells. The frequencies of spontaneously occurring DNA single strand breaks in cells grown in BrdUrd containing medium are higher than in the cells grown in normal medium and this increase depends on the amount of BU incorporated in the DNA of these cells. We have studied the extent of increase in the frequencies of SCEs due to 1 mM 3AB in several human cell lines, including those derived from patients suffering from genetic diseases such as ataxia telangiectasia (A-T), Fanconi's anemia (FA), and Huntington's chorea. None of these syndromes showed any increased response when compared to normal cells. 3AB, however, increased the frequencies of spontaneously occurring chromosomal aberrations in A-T and FA cells. 3AB does not influence the frequencies of SCEs induced by UV or mitomycin C (MMC) in CHO cells. However, it increases the frequencies of SCEs induced by ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS). Under the conditions in which 3AB increases the frequencies of spontaneously occurring as well as induced SCEs, it does not increase the frequencies of point mutations in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus. 3AB does not influence the amount of repair replication following dimethylsulphate (DMS) treatment of human fibroblasts, or UV irradiated human lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"8 4 1","pages":"227-42"},"PeriodicalIF":0.0,"publicationDate":"2020-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75490407","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":"Possible relationship between tissue distribution of DNA adducts and genotoxicity of food-derived heterocyclic amines.","authors":"S S Thorgeirsson,&nbsp;C D Davis,&nbsp;H A Schut,&nbsp;R H Adamson,&nbsp;E G Snyderwine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During the past decade and a half, a number of potent mutagens belonging to the class of heterocyclic aromatic amines (HCA) have been isolated and identified from cooked fish, beef, fowl and other meat, and from beef extracts. Several of these HCA mutagens have also been found to be carcinogenic in rodent bioassays, and one of these compounds, 2-amino-3-methylimidazo-[4,5-f]-quinoline (IQ), has recently been found to cause hepatocellular carcinoma in cynomolgus monkeys. The potential etiological role of these mutagens and carcinogens in human cancer prompted us to evaluate the genotoxicity of these compounds in both nonhuman primates and rodents, with particular emphasis on the formation and tissue distribution of DNA adducts. We selected three compounds for this study based on several factors including chemical structure, mutagenic activity in vitro, concentration in cooked food, and carcinogenic activity in the rodent test system. These were IQ, 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine (PhIP). To maximize the sensitivity of the DNA adduct measurements, we have employed the 32P-postlabeling method to analyze levels and tissue distribution of DNA adducts derived from IQ 8-MeIQx, and PhIP. We have measured DNA adduct formation for all three compounds in various tissues and white blood cells of monkeys following both acute and chronic administration. Both IQ and PhIP form high levels of adducts in a number of organs, particularly liver, kidney, and heart. In contrast, administration of 8-MeIQx to the cynomolgus monkeys results in the formation of only low adduct levels with many tissues showing no detectable levels of adducts. Studies in rodents have also shown that IQ and PhIP from DNA adducts in a number of organs in addition to those that are targets for carcinogenic effects of these agents. Although high DNA adduct levels of HCA are generally found in target organs for HCA induced carcinogenesis the widespread distribution of the adducts in organs not associated with the carcinogenic effects suggest that HCA exposure may be a possible etiological factor in cardiovascular diseases and other degenerative ailments.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"23 ","pages":"85-92"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19812303","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":"Hepatitis B and C viruses in hepatitis B surface antigen negative hepatocellular carcinoma patients.","authors":"C Bréchot,&nbsp;M Minami,&nbsp;S De Mitri,&nbsp;P Paterlini","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) has been recognized for a long time as a major etiological factor in hepatocellular carcinoma (HCC) in endemic regions. HCCs occurring in Europe, an area with a low prevalence of HBV infections, are in fact also linked to chronic HBV infection, as revealed by the detection of the viral genome and HBV X gene transcripts in the tumor. There is also a significant association with hepatitis C virus (HCV) infection and a complex interplay may occur between HBV, HCV, and other environmental factors such as alcohol, as well as genetic factors. Preliminary evidence exists for a role of HCV in liver carcinogenesis even without the pre-existing cirrhosis.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"199-209"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19840407","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":"Surgical treatment of hepatocellular carcinoma.","authors":"T Kosuge","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"265-70"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19840414","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":"Preneoplastic lesions in chronic hepatitis C.","authors":"S N Thung,&nbsp;P Hytiroglou,&nbsp;I Fiel,&nbsp;N Theise","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A significant proportion of patients with hepatocellular carcinoma (HCC) are infected with hepatitis C virus (HCV). This finding suggests that HCV infection is a major risk factor for the development of HCC. It is presently unclear whether HCV has a direct oncogenic effect on infected hepatocytes or whether continuous cell regeneration due to the chronic necroinflammatory process predisposes hepatocytes to mutations and malignant transformation. Except for rare cases, HCC in chronic HCV infection is always associated with cirrhosis. We examined a series of 138 consecutive cirrhotic livers with chronic hepatitis C that had been removed during transplantation for evidence of macroregenerative nodules (MRNs), liver cell dysplasia of large and small cell types, and HCC. MRNs and liver cell dysplasia are currently considered to be precursors of HCC. HCCs were present in 38 livers (28%) and were multifocal in half of the cases. MRNs were identified in 34 livers (25%). The number of MRNs ranged from 1 to 5 in 28 patients and was greater than 5 in 6 patients. In 14 of 34 livers with MRNs, there were associated HCCs (41%). Eight MRNs contained microscopic HCC. No microscopic HCC was found outside of MRNs; however, grossly apparent HCCs might have arisen from MRNs. Large liver cell dysplasia (LLCD) was frequently observed. It was present in 97 livers (70%) with or without MRNs and/or HCCs. Small liver cell dysplasia (SLCD) was seen in 8 livers with MRNs and/or HCCs and in 1 liver without MRN and HCC. These findings suggest that in chronic HCV infection, multifocal HCC is often found. MRN may represent one pathway in hepatocarcinogenesis. LLCD, similar to that found in chronic hepatitis B virus (HBV) infection, is a common finding in HCV-infected livers with cirrhosis, and appears not to be directly related to the development of HCC. SLCD is rarely seen, but may represent an important step in malignant transformation.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"171-8"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19841148","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":"Hepatitis C and its sequelae: the biology of hepatitis C virus and implications for its control.","authors":"R H Purcell","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma is one of the most important cancers worldwide and at least two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be etiologically associated with its development. Regardless of the nature of this association, control of these two viruses would likely be effective in the prevention of hepatocellular carcinoma. The control of HBV is achievable through proper utilization of highly effective vaccines against HBV. However, the development of useful vaccines against HCV will require more knowledge about the genetic and serologic heterogeneity of this virus and the nature of the host's immune response to it.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19841849","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":"Translation of hepatitis C virus genome.","authors":"N Ali,&nbsp;C Wang,&nbsp;A Siddiqui","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry through the 5' end (5' noncoding region) in a cap-independent fashion. The relatively long stretch of this noncoding region contains multiple initiation codons that are apparently not used for translation. Translation of the HCV polyprotein is initiated instead from an AUG located at nt 342. Using computer-assisted analysis (and subsequently substantiated by enzymatic probing), a complex secondary and tertiary structure of the 5' noncoding region (5'NCR) has been predicted. Based on an RNA folding model proposed by Brown et al. (1992), a detailed mutational analysis carried out identified the key secondary structural regions that are of functional significance in translational control. Maintenance of a helical structural element relevant to an oligopyrimidine tract is essential for internal initiation. A putative coaxial stacking or a pseudoknot structure upstream of the initiator AUG seems to be central to an internal ribosome entry site (IRES)-mediated translation of the HCV RNA genome.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"99-110"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19841859","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":"Induction of cytochrome P4501A isozymes by heterocyclic amines and other food-derived compounds.","authors":"M I Kleman,&nbsp;E Overvik,&nbsp;L Poellinger,&nbsp;J A Gustafsson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The cytochrome P-4501A1 and P-4501A2 enzymes are involved in the metabolic activation of a number of environmental precarcinogens including the food-derived heterocyclic amines. These compounds also induce CYP1A activity in rats, a feature they have in common with several of the xenobiotics (most notably benzo[a]pyrene) which are metabolically activated by the cytochrome P-4501A isozymes. Using an in vitro DNA binding assay and an in vivo functional (transactivating) assay, we have found that the cytochrome P-4501A1 induction response produced by the heterocyclic amines is mediated by the intracellular dioxin receptor. In the absence of ligand, the receptor is inactive and does not bind DNA. In this report we demonstrate a correlation between activation of DNA binding activity of the receptor by the heterocyclic amines and their ability to induce transcription from a minimal dioxin-response element-driven promoter construct. However, relatively high doses of these compounds are required to produce these effects. Therefore, despite a relatively high dietary intake of heterocyclic amines as compared to other cytochrome P-4501A1-inducing substances, the heterocyclic amines most probably only play a minor role in the induction of this enzyme activity. In contrast to the heterocyclic amines, indolo derivatives found in cruciferous vegetables exhibit high affinity for the dioxin receptor and represent potent activators of the DNA binding activity of the receptor. The indolo derivatives are therefore likely to have a larger impact than the heterocyclic amines on human CYP1A1 activity.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"23 ","pages":"163-71"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19812229","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":"Identification of new mutagenic heterocyclic amines and quantification of known heterocyclic amines.","authors":"K Wakabayashi,&nbsp;I S Kim,&nbsp;R Kurosaka,&nbsp;Z Yamaizumi,&nbsp;H Ushiyama,&nbsp;M Takahashi,&nbsp;S Koyota,&nbsp;A Tada,&nbsp;H Nukaya,&nbsp;S Goto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) was mutagenic, inducing 180 revertants of Salmonella typhimurium TA98 per 100 micrograms with S9 mix and was formed by heating a mixture of creatine, tyrosine and glucose. It was detected in broiled beef at a level of 21.0 ng per g of broiled beef, which is comparable to the level of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Two new mutagens were isolated from bacteriological-grade beef extract using a new Salmonella tester strain, YG1024, which has a much higher O-acetyltransferase level than TA98. These mutagens were identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-g]quinoxaline (4-CH2OH-8-MeIQx) and 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline(7,9-DiMeIgQx++ +). The amounts of these mutagenic heterocyclic amines (HCAs) in beef extract were 6.0 ng and 53 ng per g of beef extract, respectively. 4-CH2OH-8-MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per microgram with S9 mix, while 7,9-DiMeIgQx induced 13,800 and 670 revertants of YG1024 and TA98, respectively, per microgram in the presence of S9 mix. The levels of nine previously reported HCAs in cooked meats and fish and in beef extract were determined quantitatively. The level of PhIP was highest (0.56 approximately 69.2 ng/g), followed by that of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (0.64 approximately 6.44 ng/g), and those of other HCAs were 0.03 approximately 2.50 ng/g. Mainstream smoke condensates of five Japanese brands of cigarettes contained four HCAs, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), at levels of 0.02 approximately 13.5 ng per cigarette and sidestream smoke condensates of two brands of cigarettes contained these HCAs at levels of 0.14 approximately 2.72 ng per cigarette. PhIP was not detected in any sample of mainstream or sidestream smoke condensate.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"23 ","pages":"39-49"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19812982","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":"Structure and selection of hepatitis B virus variants during the natural course of infection and interferon therapy.","authors":"S Günther,&nbsp;S Miska,&nbsp;H Meisel,&nbsp;H Will","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The consequences of hepatitis B virus (HBV) infection range from asymptomatic transient and chronic infections to mild and severe forms of hepatitis up to the development of liver cirrhosis and hepatocellular carcinoma. Immune-mediated destruction of infected liver cells plays a major role in HBV pathogenesis. Escape from immune-recognition by changing the antigenic make-up of HBV or by preventing the expression of some viral proteins leads to the emergence of viral variants. Variants can harbor mutations in the pre-core/core gene (pre C/C) or the preS/S gene, either of which can play a role in immune escape, viral persistence, and pathogenesis. A novel method has been developed to facilitate identification and functional analysis of full-length variant genomes of HBV, with implications for HBV diagnosis and therapy.</p>","PeriodicalId":77594,"journal":{"name":"Princess Takamatsu symposia","volume":"25 ","pages":"211-20"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19840408","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}