Showing papers on "Chromosome breakage published in 1979"
TL;DR: Eight X-linked recombination-defective meiotic mutants and 12 X- linked mutagen-sensitive mutants of Drosophila melanogaster have been examined cytologically in neuroblast metaphases for their effects on the frequencies and types of spontaneous chromosome aberrations.
Abstract: Eight X-linked recombination-defective meiotic mutants (representing five loci) and 12 X-linked mutagen-sensitive mutants (representing seven loci) of Drosophila melanogaster have been examined cytologically in neuroblast metaphases for their effects on the frequencies and types of spontaneous chromosome aberrations. Twelve mutants, representing five loci, significantly increase the frequency of chromosomal aberrations. The mutants at these five loci, however, differ markedly both in the types of aberrations produced and the localization of their effects along the chromosome. According to these criteria, the mutants can be assigned to four groups: (i) mutants producing almost exclusively chromatid breaks in both euchromatin and heterochromatin; (ii) mutants producing chromatid and isochromatid breaks in both euchromatin and heterochromatin; (iii) mutants producing chromatid mutants producing chromatid and isochromatid breaks clustered in the heterochromatin.
86 citations
TL;DR: It is shown here that transplacental exposure to chemicals which require metabolic activation can cause chromosome breakage, indicated by micronucleus formation, in mouse fetal tissue, thus providing a method for quantitative assessment of risks inherent in prenatal exposure to certain classes of carcinogenic and mutagenic chemicals.
Abstract: EXPOSURE to chromosome-damaging chemicals during prenatal development is particularly hazardous, since stem-cells needed to support tissue maintenance throughout life may then be at risk. Lesions in fetal cells lead to cancer in early life, and in germ-cell lineages, contribute to increased inherited abnormalities. Chemicals can be screened for chromosome-breaking potential in vivo by the micronucleus test1 which measures frequencies of acentric chromosome fragments2. Micronuclei are usually scored in polychromatic erythrocytes from adult rodent bone-marrow. This short-term test is claimed to be as reliable as the more laborious analysis of metaphase chromosomes for chemically-induced visible aberrations3,4. The reactive forms of chromosome-damaging chemicals are often metabolites formed within tissues of exposed individuals. Short-term methods to determine genome-damaging potential must incorporate realistic activating systems if derived risk-estimates are to be meaningful. Although fetal organs contain enzymes which activate mutagenic/carcinogenic chemicals5, the micronucleus test has not previously been applied to transplacental exposure. Adult bone marrow has limited activation capacity and short lived mutagens/carcinogens formed in other tissues may not survive in the circulation, so false-negative results can be obtained. Late in gestation, blood cells develop in the fetal liver, alongside hepatocytes which metabolise premutagens/carcinogens to active forms. We show here that transplacental exposure to chemicals which require metabolic activation can cause chromosome breakage, indicated by micronucleus formation, in mouse fetal tissue. The dose dependence of this intrauterine genetic damage can be measured, thus providing a method for quantitative assessment of risks inherent in prenatal exposure to certain classes of carcinogenic and mutagenic chemicals.
78 citations
TL;DR: It is concluded that 18 compounds induced significant increase in chromosome damage and are potentially harzardous and should be studied further in detail.
Abstract: We have surveyed the clastogenic potential of 12 different groups of stains and dyes totalling 48 compounds We observed that 18 compounds induced significant increase in chromosome damage Most of them were also found to be mutagenic, carcinogenic, or toxic in other reported studies However, no significant studies were reported on six of them It is concluded that these agents are potentially harzardous and should be studied further in detail
60 citations
TL;DR: The proportion of breaks accompanied by S CEs is related to the overall SCE frequency and falls into the range predicted on the basis that breaks and SCEs occur independently.
Abstract: Studies of classical chromosome aberrations and sister-chromatid exchanges (SCEs) suggest independ mechanisms for the two events despite some common features. Examination of chromosome breakage caused by X-rays, visible light, and viruses has shown that few chromatid breaks are accompanied by SCEs at the sites of breaks. No similar observations were available for chemically induced breaks, but it has been reported that rat chromosomes exposed to dimethylbenzanthracene (DMBA) contained a preponderance of both aberrations and SCEs in certain specific regions, implicating a common process in their formation. These conclusions were drawn from a comparison of breaks induced in vivo with SCEs induced in vitro. However, we used 7 chemical mutagens to induce both chromatid breaks and SCEs in “harlequin” chromosomes of cultured rat and Chinese hamster ovary (CHO) cells and found that 25% of the 914 breaks scored were associated with SCEs. The proportion of breaks accompanied by SCEs is related to the overall SCE frequency and falls into the range predicted on the basis that breaks and SCEs occur independently. The reported association between sites for SCEs and aberrations also reflects secondary factors, such as induction of SCEs and aberrations during DNA synthesis in late replicating regions of the chromosomes.
59 citations
TL;DR: Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity, and a clear dose-response relation between SCE rate and cis- DDP concentration was observed.
Abstract: cis -Dichlorodiamminoplatinum-II ( cis -DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of ( cis -DDP) was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis -DDP. Significant increases in SCE rate were observed at 0.25 μg/ml and higher, showing a clear dose-response relation between SCE rate and cis -DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis -DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis -DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis -DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.
49 citations
TL;DR: Investigation of chromosome breakage in peripheral lymphocytes, cultured fibroblasts and long-term lymphoblastoid cell lines in patients with ataxia telangiectasia suggests that selection pressures, in vivo or in vitro, or both, act differently on the expression of chromosomal instability in these various cell types.
Abstract: Chromosomal breakage in peripheral lymphocytes, cultured fibroblasts and long-term lymphoblastoid cell lines was investigated in five hitherto undescribed patients with ataxia telangiectasia (AT). Increased chromosomal instability was observed in lymphocytes and fibroblasts, and clones possessing a Dq+ marker were observed. Breakage rates were significantly higher in the fibroblasts than in the lymphocytes of AT patients or in similar tissues from patients with Bloom syndrome or Fanconi anemia. However, chromosome breakage in lymphoblastoid lines established from these five AT patients and six others did not differ from controls. These observations suggests that selection pressures, in vivo or in vitro, or both, act differently on the expression of chromosomal instability in these various cell types.
47 citations
Journal Article•
TL;DR: The ability to distinguish readily between the three genotypes in an in vitro stress system that measures the response of the cells to a clastogenic agent makes available a test for the prenatal and postnatal detection of the FA gene.
Abstract: We have studied the pattern of chromosome instability in cultured fibroblasts and fetal membrane cells from a fetus aborted by an individual with a history of a previous child affected with Fanconi anemia (FA). These cells exhibited a low level of spontaneous chromosome instability. Upon treatment with diepoxybutane (DEB), chromosome breakage increased to a level comparable to that reported earlier in DEB-treated FA heterozygous cells. Cultured cells derived from chromosomally normal fetuses which served as controls did not show DEB-induced chromosome breakage. This observation suggests that the fetus studied is heterozygous for the FA gene. The ability to distinguish readily between the three genotypes (homozygous FA, heterozygous FA, and normal) in an in vitro stress system that measures the response of the cells to a clastogenic agent makes available a test for the prenatal and postnatal detection of the FA gene.
41 citations
TL;DR: Analysis of the size distribution of mwh clones produced byThese mutants suggests that most chromosome instability caused by these mutants is the consequence of chromosome breakage; in the presence of mus-105 and mus-109 alleles a small fraction of the mWh clones are produced by an event (mitotic recombination, mutation, nondisjunction) that produces euploid clones.
Abstract: The effects of 13 mutagen-sensitive (mus) mutants (representing seven loci) on mitotic chromosome stability in nonmutagenized cells have been examined genetically. To do this, mus-bearing flies heterozygous for the recessive somatic-cell marker, multiple wing hairs (mwh), were examined for increased frequencies of mwh clones in the wing blade. Mutants at the mus-103, mus-104 and mus-106 loci do not affect the frequency of mwh clones, while mus-101, mus-102, mus-105 and mus-109 alleles cause increases in the frequency of mwh clones. These data show that the wild-type alleles of latter four loci specify functions that are required for chromosome stability in nonmutagenized cells. Analysis of the size distribution of mwh clones produced by these mutants suggests that most chromosome instability caused by these mutants is the consequence of chromosome breakage; in the presence of mus-105 and mus-109 alleles a small fraction of the mwh clones are produced by an event (mitotic recombination, mutation, nondisjunction) that produces euploid clones. To inquire whether any of the extant alleles of the mus-101, mus-102, mus-105 and mus-109 loci might be leaky alleles of loci that carry out essential mitotic functions, chromosome stability in females homozygous for alleles of these loci has been compared to that of females carrying one dose of a mutant over a deficiency for that mus locus. These comparisons show that the extant alleles at the mus-101, mus-109 and mus-105 loci are all leaky mutants. It is suggested that all three of these loci may specify essential mitotic functions.
40 citations
TL;DR: Results show that hybrid release of mutator activity does occur as the result of hybridisation, producing a severalfold increase in the frequency of mutation, suggesting hybrid release may be a major mechanism in the induction of genetic variation in natural populations and so be a driving force in evolution.
Abstract: IT has been suggested by Grant1–2 that mutation and hybridisation may not be independent of one another as sources of genetic variation in natural populations. Indeed, it has been shown in both plants and animals3–8 that hybridisation can stimulate the production of new mutations and chromosome breakage events. The possible role of intraspecific hydridisation in inducing genetic change has recently been discussed in various contexts, especially in relation to the action of mutator genes in natural populations1,2,9–11. We have previously suggested that mutator factors, which are known to induce both visible and lethal mutations and chromosome breakage, are commonly present in natural populations of Drosophila melanogaster. Within sub-populations, however, these mutators are genetically suppressed. On hybridisation between subpopulations, genetic suppression breaks down, resulting in the release of mutator activity and, hence, in an explosive increase in genetic variation. Clearly, these explosions of mutation, which have been documented in some natural populations12,13, might have an important role in evolution and speciation. Here, we test this hypothesis of ‘hybrid release’ directly by determining whether intraspecific hybridisation increases the frequency of mutation above that found in the sampled natural population. Our study differs significantly from other assays of mutator gene effect14–16 in that mutation frequencies before and after hybridisation are compared directly. The results show that hybrid release of mutator activity does occur as the result of hybridisation, producing a severalfold increase in the frequency of mutation. Thus, hybrid release may be a major mechanism in the induction of genetic variation in natural populations and so may be a driving force in evolution.
34 citations
TL;DR: The drug D-penicillamine, a close analog of L-cysteine, gave an apparent therapeutic response in several patients and reduced the chromosome breakage frequency in the lymphocytes of these patients in vitro and in vivo.
Abstract: The incidence of chromosome breakage was found to be elevated in 42 patients with Crohn's disease. This phenomenon was much more striking in cultures set up with TCM 199 than in cultures set up with RPMI 1629 rich in L-cysteine. The drug D-penicillamine, a close analog of L-cysteine, gave an apparent therapeutic response in several patients and reduced the chromosome breakage frequency in the lymphocytes of these patients in vitro and in vivo.
32 citations
TL;DR: A regional map of the five human genes on chromosome 12 was established and the statistical map, in general, agrees with the cytogenetic map and further localizes PEPB to 12q21.
Abstract: Karyological analysis was performed on a series of human-Chinese hamster cell hybrids containing deletions of human chromosome 12. Chromosome breakage was produced by treatment of the cells with either X-rays or 5-bromodeoxyuridine and near-visible light. The hybrid clones were analyzed for the presence or absence of the following five human gene markers known to be located on chromosome 12: triosephosphate isomerase-1 (TPI1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase-B (LDHB), serine hydroxymethyltransferase (SHMT), and peptidase-B (PEPB). Based on the correlation between the isozyme markers and karyological analysis of these clones, a regional map of the five human genes on chromosome 12 was established. The linear order for these genes is: pter-TPI1-GAPDH-LDHB-centromere-SHMT-PEPB-qter. The locations of these genes are: TPI1, GAPDH, LDHB: pter leads to p12; SHMT: q12 leads to q14; PEPB: q14 leads to qter. Statistical analysis similar to that of Goss and Harris (1975, 1977a, b) has been performed on the segregation data in the hybrid clones. The statistical map, in general, agrees with the cytogenetic map and further localizes PEPB to 12q21.
TL;DR: These experiments separate the clastogenic effect of the carcinogen from its cytotoxic effect, and show genetic differences in susceptibility of cells to carcinogen-induced chromosome damage.
TL;DR: It is proposed that chromosome aberrations in BS mainly result from breaks in S—G2, including possible U-type rejoining of sister chromatid exchanges, and not on the basis of previous mitosis.
Abstract: The occurrence of chromosome breaks and reunion of sister chromatids in lymphocytes of two patients with Bloom's syndrome has been compared with those found in X-rayed and control cells. The distribution of breaks in BS is non-random both between and within chromosomes, the centric regions of certain chromosomes being preferentially involved. The following working hypotheses are put forward: When chromosome breaks in human lymphocytes occur in G0— G1, practically no sister chromatid reunion (SCR) takes place, whereas ends created by an S—G2 break show a considerable tendency to SCR. We propose further that chromosome aberrations in BS mainly result from breaks in S—G2, including possible U-type rejoining of sister chromatid exchanges. Fragments extra to an intact chromosome complement result from a chromatid break or an asymmetrical chromatid translocation in a previous mitosis.
TL;DR: BPL induced translocations in stored spermatozoa when injected, but not when fed, and the breakage capacity of BPL was one order of magnitude lower than that of MMS, when a comparison was made on the basis of equal recessive-lethal frequencies.
Abstract: Beta-propiolactone (BPL) was tested for the induction of sex-linked recessive lethals and autosomal translocations in Drosophila melanogaster. The compound was administered to adult males either by oral application or by abdominal injection. When injected, BPL was a potent inducer of sex-linked recessive lethals. When BPL was given by feeding, its mutagenic activity was detectable only when the flies were starved and when the BPL-containing solutions were renewed several times. Nevertheless, the recessive-lethal frequency was one order of magnitude higher with injection. This difference in effects is attributed to (1) rapid decomposition of the compound in aqueous feeding solutions, and to (2) rapid degradation in vivo which restricts the activity of BPL mainly to the site of application. These data are compared with other studies in which both routes of application were applied. BPL induced translocations in stored spermatozoa when injected, but not when fed. This finding seems a logical consequence of (1) the difference in effectiveness of the two routes of application for BPL, and (2) the existence of different LECs for mutation induction (recessive lethals) and for chromosome breakage (translocations). In Drosophila, the breakage capacity of BPL was one order of magnitude lower than that of MMS, when a comparison was made on the basis of equal recessive-lethal frequencies.
TL;DR: Two Japanese brothers are described, with particular emphasis on their chromosomal constitution, which is inherited in an autosomal recessive manner, with an incidence of about 1:10,000 live births and equal distribution between males and females.
Abstract: In the monograph by Seckel,1the phenotype of "bird-headed" dwarfs has been delineated in detail. Main features include proportionate dwarfism with low birth weight, microcephaly with simplified gross cerebral structure, mental retardation, typical narrow face with micrognathia, large eyes, and beak-like nose. Numerous skeletal and genitourinary anomalies have been described. The syndrome is inherited in an autosomal recessive manner, with an incidence of about 1:10,000 live births and equal distribution between males and females. This report describes two Japanese brothers, with particular emphasis on their chromosomal constitution (Figure). Report of Cases.—Case1.—This boy was 8 years old at the time of examination. He was the result of a normal pregnancy and delivered at term in the breech position. The mother was 31 years old and the father was 34 years old at the time of his birth. Birth weight was 1,040 g. At 8 years of age,
TL;DR: It is shown that extract of green chillies (Capsicum annum) produces irrepairable damage in root tip cells of onion, and it is advisable to limit the use of chillies in food as far as possible.
Abstract: In a cytogenetic study on dividing root tip cells of onion, extract of green chillies was evaluated for cytotoxic and mutagenic effects in comparison with an untreated control group.The occurrence of achromatic lesions or ‘gaps’, chromosome breakage, chromosome clumping etc. were noticed in the treated cells. The frequency of abnormal metaphases was determined in the different treatments.The present study has shown that extract of green chillies (Capsicum annum) produces irrepairable damage in root tip cells of onion. It is advisable to limit the use of chillies in food as far as possible.
TL;DR: Mixed lymphocyte cultures were employed to assess the degree of spontaneous chromosome fragility in patients with retinoblastoma and there was no difference between the patients and their controls.
Abstract: Mixed lymphocyte cultures were employed to assess the degree of spontaneous chromosome fragility in patients with retinoblastoma. There was no difference between the patients and their controls. If chromosome instability plays a role in the inherited tumour, more sensitive methods need be employed to elucidate it.
TL;DR: No difference was found between the heterozygotes and the control group, except for one control (aged 46) who had a significantly higher number of chromosome aberrations than the others.
Abstract: The frequency of chromosome aberrations in the lymphocytes of three established heterozygotes for the Bloom's syndrome gene (ages 67, 57, 46) was compared to that in controls (ages 68, 67, 61, 46, 34). The main part of the study was done on coded slides. No difference was found between the heterozygotes and the control group, except for one control (aged 46) who had a significantly higher number of chromosome aberrations than the others.
TL;DR: Results indicate the sensitivity of this scheme for the detection of events induced by x-rays and various chemicals and positive results have been obtained with the known mutagens EMS and x-radiation.
Abstract: A nondisjunction and chromosome breakage screening system devised by Craymer and modified in our laboratory, involves an X;Y translocation with the short arm of the Y (Ys), marked with the wild typ...
Journal Article•
TL;DR: Serial studies may help identify infants and young children at risk to develop this type of constitutional marrow hypoplasia.
Abstract: Anticipation of Franconi's anemia prior to the development of overt marrow aplasia may prevent some morbidity and mortality from infectious and hemorrhagic complications. A presumptive diagnosis was made in a firstborn child and radial anomalies, small size, elevated fetal hemoglobin, intermittent excessive chromosome breakage and elevated T-antigen expression in fibroblasts infected with Simian virus 40. Serial studies may help identify infants and young children at risk to develop this type of constitutional marrow hypoplasia.
TL;DR: Quantitative and qualitative studies on the induction of no-disjunction and related phenomena can be carried out using the germ cells of Drosophila using X-Irradiation and cold-shock treatments, producing different spectra of nondisjunction in oocytes.
Abstract: Quantitative and qualitative studies on the induction of no-disjunction and related phenomena can be carried out using the germ cells of Drosophila. X-Irradiation breaks chromosomes and cold-shock ...
TL;DR: The narcotic antagonist, Naltrexone, was tested for mutagenicity in Drosophila and results from large-scale experiments testing for chromosome breakage and nondisjunction were negative.
Abstract: The narcotic antagonist, Naltrexone, was tested for mutagenicity in Drosophila. The frequency of sex-linked recessive lethals at a non-toxic dose of 10 mg/ml was 0.43% (42 lethals in 9697 X-chromosomes tested) and 0.16% (19/11536) in the controls. The difference is statistically significant (P < 0.001). Results from large-scale experiments testing for chromosome breakage and nondisjunction were negative.
TL;DR: It is hypothesized that the excessive chromosome damage observed in these cell cultures is related to the permanent production of virus, thus indicating a chromosome breaking effect of endogenous viruses.
Abstract: A considerable increase in chromatid and chromosome breaks, as well as excessive fragmentation and “pulverization” of whole metaphase plates was observed in embryonic fibroblast cultures from New Zealand black mice. A C-type RNA virus with a xenotropic host range was isolated from the supernatant fluid of co-cultures of NZB cells and heterologous permissive cells (SIRC cell line). One of the NZB cultures produced this virus without amplification by co-cultivation after spontaneous transformation of the cells. NZB cells are supposed to lack normal restriction of complete xenotropic virus expression and to release this endogenous virus spontaneously at a high level. It is hypothesized that the excessive chromosome damage observed in these cell cultures is related to the permanent production of virus, thus indicating a chromosome breaking effect of endogenous viruses.
TL;DR: The compound, methadone, used as a modality in the treatment of heroin addiction, was tested for mutagenic activity in germ cells of Drosophila and results were negative in tests for sex-linked recessive lethals using feeding and injection procedures.
Abstract: The compound, methadone, used as a modality in the treatment of heroin addiction, was tested for mutagenic activity in germ cells of Drosophila. Results were negative in tests for sex-linked recessive lethals using feeding and injection procedures. Similarly, results from tests for chromosome breakage and nondisjunction failed to provide evidence of a mutagenic effect.
TL;DR: In the present paper, studies on in vitro chromosome breakage induced by benzene and its metabolites as well as cadmium, lead, and chromium compounds are reviewed and inhibition of repair of radiation-induced chromosome breaks by clastogens is reported.
Abstract: Radiation-induced chromosome damage has been widely recognized and intensively studied. Recently, attention is placed on chromosome changes induced by various industrial chemicals. In case of occupational exposure to ionizing radiation, chromosome breaks are characterized as one of the most sensitive biological effects. Chromosome breaks among industrial workers who dealt with benzene, vinyl chloride monomer or styrene have also been reported. Moreover, relationship between chromosome changes and exposure to environmental lead, cadmium and mercury compounds have been studied. Ionizing radiation, benzene and vinyl chloride monomer are known also as industrial carcinogens and attention is now placed on carcinogenicity of clastogens or chromosome breaking agents. In the present paper, our studies on in vitro chromosome breakage induced by benzene and its metabolites as well as cadmium, lead, and chromium compounds are reviewed. Also, inhibition of repair of radiation-induced chromosome breaks by clastogens is reported. Significance of cytogenetic studies in industrial medicine is also discussed.