bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA sequence analysis of spontaneous hprt mutations arising in vivo in cynomolgus monkey T‐lymphocytes
Authors: Harbach P. R. , Mattano S. S. , Zimmer D. M. , Wang Y. , Aaron C. S. 
Published: February 2007

AbstractTo study the mechanisms of mutagenesis in vivo, we analyzed mutations at the hypoxanthine phosphoribosyl transferase (hprt) locus using cDNA from cynomolgus monkey T‐lymphocytes. In the present study, the spectrum of spontaneous hprt mutations arising in vivo in wild‐caught cynomolgus monkey peripheral T‐lymphocytes is described. Cells were isolated from peripheral blood, and mutant clones were selected in 6‐thioguanine, propagated, and stored frozen. cDNA was copied from hprt mRNA from a lysate of 7,000 to 20,000 cells. A 780‐base‐pairs (bp) region including the coding region was amplified by polymerase chain reaction and directly sequenced. We sequenced 40 spontaneous mutants from 11 monkeys. Of these 40 clones, 23 (57%) had base‐pair substitutions, 11 (28%) had small (<20 bp) deletions and/or insertions, and 6 (15%) had large (>20 bp) deletions and/or insertions. Of the 23 base substitutions, 13 were transitions (11 G:C → A:T, 1 A:T → G:C, and 1 tandem TT → CC) and 10 were transversions (3 G:C → T:A, 3 G:C → C:G, 2 A:T → T:A, 2 A:T → C:G). Bases 209 and 617 were apparent substitution hotspots, which have also been observed as hotspots in human hprt. In 2 clones with large insertions, the inserted bases were of intronic origin. One of these lost 272 bp from exons 2–3 and contained a 93‐bp insertion from the middle of intron 3. Two clones with small deletions and 5 clones with large deletions or insertions (7/40 or 17.5%) could be splice mutants. © 1995 Wiley‐Liss, Inc.
Mutation spectra in salmonella of chlorinated, chloraminated, or ozonated drinking water extracts: Comparison to MX
Authors: Demarini David M. , Abu‐Shakra Amal , Felton Carolyn F. , Patterson Kathleen S. , Shelton Melissa L. 
Published: February 2007

AbstractDrinking water samples were prepared in a pilot‐scale treatment plant by chlorination (Cl2), chlorami‐nation (NH2Cl), ozonation (O3), or O3 followed by Cl2 or NH2Cl; and the nonvolatile acidic organics of the raw and treated waters were extracted by XAD/ethyl acetate and evaluated for mutagenicity in Salmonella (‐S9). The extracts were 2–8 times more mutagenic in TA100 than in TA98, and the mutagenic potencies of the water extracts ranked similarly in both strains: Cl2 > O3 + Cl2 > NH2Cl > O3 + NH2Cl > O3 > raw. 3‐Chloro‐4‐(dichloro‐methyl)‐5‐hydroxy‐2(5H)‐furanone (MX), which was estimated to account for ∼‐20% of the mutagenic activity of the extracts, was shown to be the most potent compound tested thus far in a prophage‐in‐duction assay in Escherichia coli and a forward‐mutation assay in Salmonella TM677. The mutations in ∼2,000 revertants of TA98 and TA 100 induced by MX and the water extracts were analyzed by colony probe hybridization and polymerase chain reaction/DNA sequence analysis. The water extracts and MX produced similar mutation spectra, which consisted in TA100 of predominantly of GC → TA transversions in the second position of the CCC (or GGG) target of the hisG46 allele. This spectrum resembles that produced by large aromatic compounds and is distinct from that produced by alkylating agents and the semivolatile drinking water mutagen dichloroacetic acid. In TA98, MX and those water extracts resulting from the introduction of the chlorine atom produced 50–70% hotspot 2‐base deletions and 30–50% complex frameshifts (frameshifts with an adjacent base substitution—mostly GC → TA transversions as found in TA100). No other compound or mixture is known to induce such high frequencies of complex frameshifts. These results suggest that MX and “MX‐like” compounds (possibly halogenated aromatics, such as halogenated polycyclic aromatic hydrocarbons) account for much of the mutagenic activity and specificity of the nonvolatile organics in drinking water and that these halogenated organics are especially capable of promoting misincorporation by the DNA replication complex. This study provides further evidence that the mutation spectrum of a complex mixture reflects the dominance of one or a few classes of chemical mutagens within the mixture. © 1995 Wiley‐Liss, Inc.This article is a US Government work and, as such, i s in the public domain in the United States of America.
Enhancement of SCE frequency by alpha‐naphthoflavone in cultured lymphocytes in relation to environmental factors
Authors: Sbrana Isabella , Luccini Antonella , Landi Stefano , Barale Roberto 
Published: February 2007

AbstractOne hundred and nine healthy subjects living in an urban area of Tuscany were monitored using sister chromatid exchange (SCE) analysis on lymphocytes cultured in standard or alpha‐naphthoflavone (ANF)‐supplemented medium in order to collect the most complete data possible for those constitutional and environmental factors with which genotoxic risk can be associated. ANF genotoxicity depends on its metabolic activation by cellular P‐450 monooxygenase systems whose activity can be modulated by exposure to carcinogenic but nongenotoxic xenobiotics. Lymphocytes grown in standard conditions showed a significant increase of SCE frequency associated with smoking habits and age. Although the addition of ANF caused an upward shift of SCE frequency in all subjects, smokers, coffee drinkers, and blue‐collar workers showed a significantly higher SCE level; this suggests that potential risk factors rising from a modified cell metabolism are present in these categories. These results indicate that in vitro ANF treatment of lymphocytes could be a useful tool in the detection of environmental exposure to those classes of chemicals involved in metabolic activation of promutagens. © 1995 Wiley‐Liss, Inc.
Alkaline single cell gel (comet) assay and genotoxicity monitoring using bullheads and carp
Authors: Pandrangi Raj , Petras Michael , Ralph Steve , Vrzoc Maria 
Published: February 2007

AbstractMonitoring genotoxicity of the environment using endemic organisms as sentinels requires the development of sensitive assays. Toward this end, we explored the feasibility of applying the alkaline single cell gel (SCG) or “comet” assay. This approach involves detection, under alkaline conditions, of cell DNA fragments which, on electrophoresis, migrate from the nuclear core, resulting in a “comet with tail” formation. Tail length has been correlated with level of genotoxicant exposure in a number of organisms. The fish used in this study were benthic feeding bullheads (Ameiurus nebulosus) and carp (Cyprinus carpio). On electrophoresis of erythrocyte DNA under alkaline conditions, we found a linear increase in the tail length/core width ratio over a broad range of cyclophosphamide doses. Freshly caught bullheads from seven different sites showed a wide range of DNA damage. Bullheads from Big Creek (western Lake Erie), Hamilton Harbour (western Lake Ontario), and the Detroit River gave ratios of 3.81 to 4.65. Based on polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) levels, the sediment at these three sites is considered to be heavily polluted. Bullheads from southern Lake Huron, which is relatively clean, and from a fish hatchery in Brockport, New York, gave ratios between 1.30 and 1.40. Bullheads from Big Creek, maintained in the laboratory for 3 months, gave ratios which approached those seen in hatchery‐bred fish. Results for carp were similar. Carp from Big Creek gave ratios of about 4.50, while carp from Lake Huron and laboratory‐maintained carp gave values of 1.23 and 1.36, respectively. The results of the SCG procedure in bullheads and carp indicate that this assay is extremely sensitive and should be useful in detecting DNA damage caused by environmental contaminants. © 1995 Wiley‐Liss, Inc.
An (8;14)(q24;q11) translocation involving the T‐cell receptor α‐chain gene and the MYC oncogene 3′ region in a B‐cell lymphoma
Authors: Park James K. , McKeithan Timothy W. , le Beau Michelle M. , Bitter Mitchell A. , Franklin Wilbur A. , Rowley Janet D. , Diaz Manuel O. 
Published: February 2007

AbstractWe describe a t(8;14)(q24;q11) involving the T‐cell receptor α‐chain gene (TCRA) and the 3′ region of the MYC protooncogene in a B‐cell lymphoma. The B‐cell origin of this tumor was determined by its histological architecture, by immunophenotypic analysis, and by Southern analysis of immunoglobulin gene rearrangements. An identical fragment encompassing the translocation breakpoint junction was detected through Southern analysis using both a TCRA J and a MYC probe. The other alleles at the TCRA J and MYC loci were in the germline configuration. Restriction enzyme and nucleotide sequencing analyses revealed that the breakpoint junction on chromosome 8 lies approximately 700 base pairs (bp) downstream of the 3′ end of the third MYC exon; on chromosome 14, the break is located 12.6 kilobases (kb) downstream of the 3′ end of the Cδ fourth exon. A heptamer‐like consensus sequence on chromosome 14 adjacent to the translocation breakpoint implies the involvement of recombinase activity. However, no consensus sequences were found on chromosome 8 within 140 bp in either direction from the breakpoint. It is possible that this translocation involving MYC occurred during an attempt at an inappropriate rearrangement of the TCRA locus in a cell of B‐cell lineage.
Molecular differential pathology of rhabdomyosarcoma
Authors: Scrable Heidi , Witte David , Shimada Hiroyuki , Seemayer Thomas , Wang‐Wuu Sheng , Soukup Shirley , Koufos Alex , Houghton Peter , Lampkin Beatrice , Cavenee Webster 
Published: February 2007

AbstractTumors of the soft tissues are classified histogenetically according to their phenotypic resemblance to normal adult tissue. Here we describe molecular approaches that make it possible to distinguish between one class of these tumors, rhabdomyosarcoma, and other small‐, round‐cell tumors. We show that the ascertainment of specific genotypic changes can be used to distinguish further between the embryonal and alveolar subtypes of rhabdomyosarcoma. We tested our model in two ways: first, in a retrospective analysis of diagnostically problematic cases of undifferentiated, small‐cell tumors and, second, in a blind study of pediatric tumors. Rhabdomyosarcoma was correctly identified in all cases using this strategy alone. The underlying simplicity of the strategy used to define rhabdomyosarcoma subtypes with molecular markers suggests a model by which tumors can be unequivocally identified, which may apply equally well to other human solid tumors.
A newly established metastatic breast tumor cell line with integrated amplified copies of ERBB2 and double minute chromosomes
Authors: Band Vimla , Zajchowski Deborah , Stenman Göran , Morton Cynthia C. , Kulesa Victoria , Connolly James , Sager Ruth 
Published: February 2007

AbstractA continuous line of human mammary tumor cells, called 21MT, has been established in culture from a pleural effusion of a 36‐year‐old woman with metastatic breast cancer. The cells are epithelial as shown by morphology and expression of keratins and are mammary tumor cells as shown by expression of the HMFG‐2 antigenic determinant. The cells grow well both in DFCI‐1, a partially defined medium containing pituitary extract and 1% fetal bovine serum, and in α‐minimum essential medium (α‐MEM) supplemented with 10% serum, epidermal growth factor (EGF), insulin, and hydrocortisone. Karyotypic analysis of cells at early passage has shown the presence of rearranged (marker) chromosomes as well as aneuploidy with a net DNA content in the tetraploid range, confirmed by DNA cytofluorography, as well as double minute chromosomes in about 5% of the cells. Southern blots have revealed a 40‐fold amplification of the ERBB2 gene and a 50‐fold overexpression of its mRNA. The amplification of ERBB2 DNA was localized by in situ hybridization to one of the marker chromosomes but not to the double minutes. It is inferred, therefore, that at least two genes have been amplified in these cells.
Alteration of mitochondrial DNA in human oncocytomas
Authors: Welter Cornelius , Kovacs Gyula , Seitz Gerhard , Blin Nikolaus 
Published: February 2007

AbstractOncocytoma, a benign solid tumor, occurs in a number of organs but most frequently in the kidneys. Its oncocytes display an intensely eosinophilic cytoplasm due to presence of numerous mitochondria. Mitochondrial DNA analysis of six renal cell oncocytomas and adjacent renal tissue was performed using five restriction endonucleases. In the Hinfl restriction pattern, an additional 40 bp band was noted. This new band was demonstrated in all oncocytomas but in none of the corresponding renal tissues or additionally tested renal carcinomas. By reisolating and hybridizing this band to the mitochondrial genome, its sequence was localized within the cytochrome c oxidase subunit I gene. The data suggest that a molecular alteration of mitochondrial DNA is specific for oncocytomas, and this constitutes the first observed mitochondrial DNA change in a human solid tumor.
Molecular mapping of the oncogene MYB and rearrangements in malignant melanoma
Authors: Meese Eckart , Meltzer Paul S. , Witkowski Colette M. , Trent Jeffrey M. 
Published: February 2007

AbstractThe human cellular oncogene MYB has been mapped to 6q22–q23. Deletions and translocations involving this region of the long arm of chromosome 6 occur frequently in human malignant melanoma, and there are anecdotal reports of MYB gene rearrangements in this cancer. In the current study, Southern blotting and pulsed field gel electrophoresis (PFGE) have been performed to determine whether MYB or its flanking regions are commonly altered in malignant melanoma. Southern blotting failed to document obvious rearrangement of the MYB gene in 15 cases studied. To extend analysis of the MYB region, a long‐range restriction map was established by PFGE. This map was then linked to the known restriction map of frequent cutting enzymes. Based on the mapping data and analysis of the MYB region in melanomas, Clal tissue‐specific variation due to methylation was demonstrated. Also, two melanomas (containing alterations in band 6q13) also demonstrated by PFGE a unique restriction fragment for the MYB gene. These results extend significantly the physical map surrounding the MYB locus and provide further evidence for the rearrangement of chromosome 6 in malignant melanoma.
Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement‐positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes
Authors: Dubé Ian , Dixon Julie , Beckett Teresa , Grossman Abraham , Weinstein Martha , Benn Peter , McKeithan Timothy , Norman Con , Pinkerton Peter 
Published: February 2007

AbstractWe report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.
Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system
Authors: Biegel Jaclyn A. , Rorke Lucy B. , Packer Roger J. , Sutton Leslie N. , Schut Luis , Bonner Kathy , Emanuel Beverly S. 
Published: February 2007

AbstractWe have prepared karyotypes from 22 primitive neuroectodermal tumors (PNETs) from pediatric patients ranging in age from 10 months to 16 years. Twenty‐one cases were newly diagnosed, primary, posterior fossa tumors. One case was a recurrent tumor in a patient previously treated with radiation. Cytogenetic results were obtained from direct preparations and/or short‐term (1–10 day) culture. Three tumors had apparently normal karyotypes. Nineteen tumors demonstrated numerical and/or structural abnormalities. The most frequent structural chromosomal changes were deletions and nonreciprocal translocations. Four tumors contained double minutes. Several chromosomes appear to be nonrandomly involved in PNETs. These include chromosomes 5, 6, 11, 16, 17, and a sex chromosome. The most consistent change, however, was an i(17q), present in one‐third (8/22) of the cases. Strikingly, in three of these eight tumors, the i(17q) was the only structural abnormality observed. An i(17q) is not specific for pediatric PNETs, as it is also seen in leukemias and other solid tumors. However, in PNETs it may be primary change related to tumor development and/or progression. Clinically, there was no correlation of the cytogenetic findings with histologic features of the tumors, size of the tumor, extent of metastasis, or surgical resection.
Consistent occurrence of a 19p+ marker chromosome and loss of 11p material in ovarian seropapillary cystadenocarcinomas
Authors: Pejovic Tanja , Heim Sverre , Mandahl Nils , Elmfors Bengt , Flodérus Ulla‐Maria , Furgyik Stefan , Helm Göran , Willén Helena , Mitelman Felix 
Published: February 2007

AbstractCytogenetic analysis of short‐term cultures from 11 moderately to poorly differentiated ovarian seropapillary cystadenocarcinomas revealed clonal chromosomal abnormalities in nine tumors. Two bands were involved in structural rearrangements in more than half of the tumors. The band most frequently affected was 19p13; rearrangements giving rise to a 19p+ marker chromosome were found in seven tumors, and in four of them the 19p+ markers appeared to be identical. Structural rearrangements resulting in loss of 11p13‐11pter material were found in six tumors.
Analysis of BCR‐ABL mRNA in chronic myelogenous leukemia patients and identification of a new BCR‐related sequence in human DNA
Authors: Marcelle Christophe , Gale Robert P. , Prokocimer Miron , Berrebi Alan , Merle‐Beral Hélène , Canaani Eli 
Published: February 2007

AbstractThe Philadelphia chromosome is present in more than 95% of chronic myelogenous leukemia patients and in up to 25% of patients with acute lymphocytic leukemia. The major consequence of the aberration is the fusion of the ABL and BCR genes. The position of the breakpoint on chromosome 22 determines which species of the potential three fused mRNAs and proteins will be synthesized. We have used the polymerase chain reaction (PCR) to detect these mRNAs in 53 patients and cell lines and found that around 20% contain simultaneously two BCR‐ABL mRNAs, presumably due to a process of alternative splicing. The results also indicate that most patients in lymphocytic blast crisis of CML contain the mRNA in which bcr exon 2 is linked to ABL exon II. Finally, we identified, cloned, and characterized a BCR‐related sequence that originated from mRNA.
Two distinct mechanisms for the SCL gene activation in the t(1;14) translocation of T‐cell leukemias
Authors: Bernard Olivier , Guglielmi Paul , Jonveaux Philippe , Cherif Dorra , Gisselbrecht Sylvia , Mauchauffe Martine , Berger Roland , Larsen Christian‐Jacques , Mathieu‐Mahul Daniele 
Published: February 2007

AbstractMolecular study of a t(1;14)(p32;q11) translocation found in an acute T‐cell leukemia (Kd cells) with a relatively mature phenotype is reported. Complex DNA rearrangements were characterized in the TCRα/δ locus. Besides a productive Vα/Jα assembly found on the normal allele, two deletions within the Jα cluster were identified in the translocated allele. The translocation breakpoints involved the TCRα gene on chromosome 14 and the SCL locus on chromosome band 1p32 that was recently shown to be activated by the t(1;14) translocation of the DU 528 leukemic cell line. Significantly, both Kd and DU 528 translocation breakpoints were located at the boundaries of Dδ or Jδ segments and were clustered in a 10 kb genomic fragment of the SCL gene. The presence of recombination signal motifs (heptamer‐12/23 bp spacer‐nonamer) on both normal chromosome partners, and N nucleotide addition on both derivative chromosomes involved the recombinase system in the translocation event. The SCL locus was highly expressed as a 5 kb transcript in Kd cells and, as already reported, as a 2 kb transcript in DU 528 cells. Importantly, a 5 kb SCL transcript was also detected in immature nonlymphoid hematopoietic cells but not in normal mature T cells, suggesting that it might correspond to the normal SCL transcript. Taken together, our data support the notion that the involvement of the SCL gene in the leukemogenic process may occur through overexpression of an apparently normal transcript (Kd cells) or expression of a truncated RNA (DU 528 cells).
Unrelated clonal chromosomal aberrations in carcinomas of the oral cavity
Authors: Jin Yuesheng , Heim Sverre , Mandahl Nils , Biörklund Anders , Wennerberg Johan , Mitelman Felix 
Published: February 2007

AbstractShort‐term cultures from 12 oral squamous cell carcinomas were cytogenetically investigated. A normal karyotype was found in 3 tumors, 2 of which had many nonclonal changes. Clonal chromosome abnormalities were detected in the remaining 9 cases, in 6 of them in the form of 2 or 3 abnormal clones. In 5 cases the different clones were cytogenetically unrelated, suggesting a multiclonal origin. Numerous additional nonclonal changes were present in 4 of the 9 tumors with clonal aberrations. None of the structural aberrations, clonal or nonclonal, were found in more than one case; nor did any of the rearrangements correspond to cancer‐associated aberrations known from other tumors. The aberration breakpoints of the present series and of a previously reported tongue cancer clustered to bands 1p32, 1p22, 1p11, 1q21, 1q23, 1q25, 1q32, 1q42, 1q44, 2q31, 3p11, 4q35, 7p22, 11p15, 11q13, 12q24, and 17q25.
Sex chromosomes in a series of 79 colorectal cancers: Replication pattern, numerical, and structural changes
Authors: Muleris Martine , Dutrillaux Anne Marie , Salmon Remy Jacques , Dutrillaux Bernard 
Published: February 2007

AbstractThe cytogenetic study of a series of 79 colorectal cancers was performed with special attention to sex chromosome behavior. It was found that apart from other chromosomal changes, the early‐replicating X chromosome (Xe) was frequently duplicated in tumors from both males and females. This contrasted with a frequent loss of either the late‐replicating X (XI) in tumors from females or of the Y chromosome in tumors from males. All the detected unbalanced rearrangements resulted in a gain of the long, but not the short, arm of the X chromosome. The replication pattern of Xe chromosomes was similar to that of control tissues, whereas that of XI chromosomes was unusual. Its main characteristic was that the two major R bands of the short arm, Xp11 and Xp22, replicated too early.