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Showing papers on "Chromosome breakage published in 1970"


Journal ArticleDOI
TL;DR: A number of physical, chemical, and biological agents are known to break chromosomes, and this paper will deal primarily with chemical clastogens.
Abstract: Two news items concerning the nation's health appeared last autumn. On October 18, 1969, Health, Education and Welfare Secretary Robert H. Finch announced a ban on cyclamate-containing foods because this artificial sweetening agent causes bladder cancer in rats. One week later, the presi­ dents of three baby food companies announced they would voluntarily dis­ continue the use of the flavor-enhancer monosodium glutamate (MSG) because it produced brain damage in newborn mice. The removal of these two food additives will change the dietary habits of millions of people. Agents which cause cancer or birth defects are easily recognized, even hy the layman, as dangerous. But what about agents which cause more subtle damage such as genetic mutation or chromosome breakage. Because changes in the genes and chromosomes do not usually produce an immediate health hazard, they may go undetected for a lifetime or even for several generations. Yet, the human gene pool can become insidiously polluted. This review concerns chemical agents which break chromosomes. Early in the writing of this article, it became apparent that a term was needed for the cumbersome phrase "chromosome-breaking agent." Already introduced into medical literature were such descriptive terms as carcinogen, leu­ kemogen, mutagen, and teratogen. The word "chromosomoclastogen" is suggested; the Greek word root "-clast" means to break, fracture, or frag­ ment. (Recall the terms osteoclast and iconoclast.) In this article, an abbre­ viated, more euphonious form, "clastogen" will be used. A number of physical, chemical, and biological agents are known to break chromosomes. Physical clastogens include X rays, ultraviolet light, cold shock, magnetic fields, and sound waves. Certain genes, viruses, and protozoa are examples of biological clastogens. This paper will deal primarily with chemical clastogens. Although the effects on human chromosomes are emphasized, it will sometimes be necessary to refer to experiments on animal and plant chromosomes. These are not irrelevant. In fact, there are no known plant clastogens to which animal chromosomes have been found to be immune. Many of the chemicals cited here have been tested on human cells only

127 citations


Journal ArticleDOI
TL;DR: A statistically significant rank correlation was found between the frequency of cells with chromosome breaks and mercury concentration in subjects with increased levels of mercury in their red blood cells and in four healthy controls.
Abstract: Chromosome analysis was performed on cells from lymphocyte cultures from nine subjects with increased levels of mercury in their red blood cells and in four healthy controls. The elevated mercury levels were likely tal have originated from dietary fish with high levels of methyl mercury. A statistically significant rank correlation was found between the frequency of cells with chromosome breaks and mercury concentration. The biological significance of these findings is at present unknown.

117 citations



Journal ArticleDOI
TL;DR: Cytogenetic changes of increased chromosome breakage and satellite association were observed in the 23 patients using oral contraceptives over the 20 patients on no gestagen therapy, revealing one baby to have D/G translocation Mongolism.

48 citations


Journal ArticleDOI
TL;DR: It is suggested that the great difference in the spectrum of genetic damage observed in mammals relative to that reported for other organisms is due to differences in the repair system.
Abstract: Ethyl methanesulfonate (EMS) or methyl methanesulfonate (MMS) with a [ 14 C]alkyl label were injected intraperitoneally into (101 × C 3 H)F 1 hybrid male mice. Radiactivity levels were measured in various tissues and tissue fractions at eight time periods ranging from 15 min to 24 h after injection. Activity levels were also measured in the blood and urine, and respiration pattern analysis was carried out on exhaled 14 CO 2 . Distribution of these compounds is rapid, and approximately the injected dose w/w reaches the testis in an active form. However, EMS is rapidly hydrolyzed in vivo , and MMS is 4–6 times more effective in alkylating biological molecules. The amount of genetic damage done in the mouse (chromosome breakage) is correlated with in vivo alkylation of macromolecules. It is suggested that the great difference in the spectrum of genetic damage observed in mammals relative to that reported for other organisms is due to differences in the repair system.

45 citations


Journal ArticleDOI
15 Aug 1970-Nature
TL;DR: A similar effect is described when exogenous deoxyribonuclease is introduced into cells in the presence of hypertonic MgSO4, a modification of the method used by Wecker2 in assays of the infectivity of extracted viral nucleic acid.
Abstract: THE possibility that endogenous deoxyribonuclease might play a part in inducing chromatid breakage was suggested by our experiments describing a high incidence of chromosome breaks and rearrangements in human diploid cell strains after selective damage to lysosomes1. We describe here a similar effect when exogenous deoxyribonuclease is introduced into cells in the presence of hypertonic MgSO4. This is a modification of the method used by Wecker2 in assays of the infectivity of extracted viral nucleic acid.

27 citations


Journal ArticleDOI
TL;DR: Drosophila melanogaster population with an irradiation history (RO I) and an unirradiated control population (+60) were tested, both being derived from the Berlin wild stock; it is demonstrated that the radiosensitivity of RO I is only half that of +60, and sex-linked recessive lethals are induced at lower frequencies in RO I than in +60.
Abstract: An approach has been made to the study of genotype-dependent mechanisms which modify the response of higher organisms to ionizing radiations. A Drosophila melanogaster population with an irradiation history (RO I) and an unirradiated control population (+60) were tested, both being derived from the Berlin wild stock. RO I was given an exposure of 2100 R of X-rays in each generation; it was maintained by using treated stages 6–14 oocytes, sperm, and late spermatids. Comparisons between +60 and RO I have been made after 220 generations of irradiation. Although X-irradiation causes a reduction of fertility, equal numbers of viable offspring are produced by the 2 populations when identical culture conditions, except the irradiation, are used. At least 2 mechanisms contribute to this adaptation of ROI to X-rays: an increased oviposition rate, and a decreased radiosensitivity for the induction of “reduced egg-to-adult survival”. Data are presented on the sensitivity of stage- 7 oocytes. The dose-response relationships for the X-ray induction of dominant lethals and X-chromosome loss are probit linear in both populations. They demonstrate that the radiosensitivity of RO I is only half that of +60. In addition, sex-linked recessive lethals are induced at lower frequencies in RO I than in +60. The sensitivity differences between +60 and RO I are statistically significant. They are not due to a shift in stages sampled from the 2 populations. Their possible relation to differences in chromosome breakage events is discussed with special emphasis on the fact that nondisjunction does not contribute to the differences in induced X-chromosome loss, and that a 2-hit component, apparent for the induction of sex-linked recessive lethals in +60, disappeared in RO I.

25 citations


Journal ArticleDOI
TL;DR: Chromosome analyses were carried out on the blood leukocytes of 23 patients using diazepam and 8 controls and one patient showed chromosome breakage in 15.3 per cent of the cells examined, while Quadriradials were seen in 2 other patients and in one control.

23 citations


Journal ArticleDOI
Corey Mj, Andrews Jc, McLeod Mj, MacLean, Wilby We 
TL;DR: There is no cytogenetic evidence that d-lysergic acid diethylamide 25 given therapeutically produces chromosomal damage, and the chromosomal aberrations found after illicit use of the drug remain unexplained.
Abstract: In a prospective study of 10 patients given d-lysergic acid diethylamide 25, there was no difference in frequency of chromosome breakage between samples obtained immediately before and 24 hours after treatment. In 11 patients, treated over periods ranging from 24 hours to eight years before sampling, the frequency of chromosomal breaks did not differ from that found in untreated controls. In an in vitro study the frequency of chromosomal breaks was increased in replicate cultures from each of 10 subjects when 1 μg per milliliter of d-lysergic acid diethylamide 25 was added during the last 24 hours of culture. There is no cytogenetic evidence that d-lysergic acid diethylamide 25 given therapeutically produces chromosomal damage. The chromosomal aberrations found after illicit use of the drug remain unexplained.

23 citations



Journal ArticleDOI
TL;DR: Of 191 interspecific crosses attempted between 27 different species representing different subgenera of Lilium only 14 gave rise to seeds and only 6 of these were viable, suggesting that sterility results from genetic imbalance of the endosperm itself rather than interaction of theendosperm with either embryo or maternal tissue.
Abstract: Of 191 interspecific crosses attempted between 27 different species representing different subgenera ofLilium only 14 gave rise to seeds and only 6 of these were viable. Sterility was associated with various types of abnormality in endosperm development. Many of these irregularities involved chromosome breakage and reunion but others entailed abnormal DNA replication and chromosome coiling. In one cross the individual endosperm nuclei contained four stranded structures, the behaviour of which at division was similar to that of bivalents at meiosis. The embryo-sac ofLilium is of theFritillaria type, containing both haploid and triploid polar nuclei. As a consequence the balance between the number of chromosome sets in the embryo, endosperm and maternal tissue is 2:5:2 and not 2:3:2 as is more commonly found in diploid species. It is suggested that sterility results from genetic imbalance of the endosperm itself rather than interaction of the endosperm with either embryo or maternal tissue.

Journal ArticleDOI
TL;DR: When the chromosome aberrations induced in human leukocytes in culture with daunomycin (Dm) are analyzed with respect to sites of breakage and reunion, non-randomness is observed, both between and within chromosomes, suggesting either a site-specificity of action of the drug or site- specific sensitivity or both.
Abstract: When the chromosome aberrations induced in human leukocytes in culture with daunomycin (Dm) (0.015 μg/ml, with or without added arginine) are analyzed with respect to sites of breakage and reunion, non-randomness is observed, both between and within chromosomes. These results suggest either a site-specificity of action of the drug or site-specific sensitivity or both. Superficially, the data give an indication of the phenomenon of somatic crossing-over having occurred. However, if chromosome breakage and reunions of broken ends are considered as two events, independent of each other, the frequency of exchanges between homologues and apparent homologues is lower than the expected frequency in cases of groups involving chromosomes 6–12/X and 13/15 and almost equal to the expected frequency in cases of chromosomes 1, 2 and 3.

Journal ArticleDOI
TL;DR: Genetic data on three asynaptic mutants showed that all are monogenically controlled by recessive genes, and the value of these asynaptics in breeding and cytogenetic research is discussed.
Abstract: Genetic data on three asynaptic mutants showed that all are monogenically controlled by recessive genes. Differences in cytological abnormalities suggested that each mutant was controlled by a separate gene. The symbol, as, is proposed for these characters with the designations, as, as2, and as3.The degree of asynapsis varied from complete failure of pairing in two of the mutants to partial asynapsis in the third. Other aberrations, such as chromosome fragmentation, lagging, attenuated univalents, micronuclei, restitution nuclei, and aberrant sporad formation were observed. The value of these asynaptics in breeding and cytogenetic research is discussed.

Journal ArticleDOI
20 Jun 1970-Nature
TL;DR: The dose–effect relationship of LSD and the type of damage produced in chromosomes of leucocyte cultures of the marsupial Potorous tridactylus (rat-kangaroo), which has a few large chromosomes that make scoring of damage relatively easy and accurate, is investigated.
Abstract: Cohen, Marinello and Back1 (1967) first reported that lysergic acid diethylamide (LSD) increased chromosome abnormalities in human leucocytes. Although some later work failed to support this observation2–4, others have confirmed that LSD damages chromosomes5–10. I have investigated the dose–effect relationship of LSD and the type of damage produced in chromosomes of leucocyte cultures of the marsupial Potorous tridactylus (rat-kangaroo), which has a few large chromosomes (2 n = 12 in ♀ and 13 in ♂) that make scoring of damage relatively easy and accurate.



Journal ArticleDOI
B.L. Kaul1
TL;DR: It has been pointed out that DMSO treatments give a definite protection against the initial radiation damage rather than stimulating the process of recovery.

Journal ArticleDOI
01 Oct 1970-Genetics
TL;DR: The present study studies the influence of an intact genome of N .

Journal ArticleDOI
TL;DR: Over a three-year period levels of spontaneous chromosome breakage were consistent for each population but differed between populations, indicating that some of these meiotic irregularities are the result of spontaneous.
Abstract: A B S T R A C T Meiocytes in three morphologically similar but cytologically different wild populations of Claytonia virginica L. were examined. Over a three-year period levels of spontaneous chromosome breakage were consistent for each population but differed between populations. Random samples of inflorescences from two of the populations were treated with 0.005 % aqueous solutions of nucleic acid precursors: adenine, adenosine, thymine, thymidine, guanosine 5'-monophosphate (GMP), and cytosine 5'-monophosphate (CMP). Statistically significant increases in chromosome breakage were observed in the population with little background breakage when inflorescences were treated with adenosine, thymine, thymidine, GMP, and CMP. In the population with moderate spontaneous breakage, a significant increase was observed only in plants treated with adenosine. Breakage induced with nucleic acid precursors was similar to that which occurred spontaneously; the predominant aberration was the single bridge. THE APPEARANCE of bridges, bridges and fragments, and fragments have been reported in natural populations of Ciaytonia virginica L. by Rothwell (1959) and Lewis (1962). These aberrations were considered to be meiotic irregularities common to polyploid populations. The present study indicates that some of these meiotic irregularities are the result of spontaneous

Journal ArticleDOI
TL;DR: The inhibition of spindle activity induced by mercaptoethanol was similar to that by colchicine, but the ultrastructural changes of chromosomal fibers caused by the former were different from those by the latter.
Abstract: The effect of colchicine, mercaptoethanol, and nitrogen mustards on the pollen mother cells of Lilium have been studied at the electron microscopic and the light microscopic levels The treatment of PMCs with colchicine induced the inhibition of the spindle activity, which was caused by the dissociation of chromosomal fibers The colchicine-treated chromosomal fibers showed a number of granules corresponding to the precursors of elemental fine fibrils of the fiber Therefore, no chromosomal fibers remain to induce the chromosome movement at anaphaseThe inhibition of spindle activity induced by mercaptoethanol was similar to that by colchicine, but the ultrastructural changes of chromosomal fibers caused by the former were different from those by the latter The chromosomal fibers treated with mercaptoethanol became sticky and could not act normallyCytological effects of alkylating agent, nitrogen mustard, were lethal inducing chromosome breakage, stickiness in nuclei, and extreme alveolation of the cytoplasmThe authors would like to thank Professor Emeritus B Wada and Professor N Tanaka, University of Tokyo, for their helpful criticism of the manuscript This work was supported by the grant from the Ministry of Education of Japan

Journal Article
TL;DR: Evidence is presented which characterizes the abnormal chromosomes as a late-replicating G ring and a pericentric inversion in an early replicating B group chromosome.
Abstract: A male infant with failure to thrive was found to have a previously unreported combination of chromosomal structural abnormalities Evidence is presented which characterizes the abnormal chromosomes as a late-replicating G ring and a pericentric inversion in an early replicating B group chromosome The mechanisms of pericentric inversion and ring formation are discussed, and possible genetic consequences are noted The patient9s phenotype differed significantly from that of previously reported subjects with G rings, G deletions, and structural abnormalities of the B group This phenotypic difference could be attributed to the apparent fact that the proband9s G ring was a late replicator (G1) and earlier cases were not, on to the seeming variability in ring size which suggested partial trisomy/partial monosomy, or perhaps to the probability that the abnormal B chromosome was pericentrically inverted rather than deleted The question of the etiologic significance of broken parental chromosomes must be raised, although more study is needed in the area of chromosome breakage, its relationship to abnormal progeny, and the possible role of environmental agents, eg, drugs and irradiation

Journal ArticleDOI
TL;DR: Linearship between treatments and cytological aberrations was shown and the nature of abnormalities in metaphase and early anaphase cytological effects and origin of different abnormal configurations were explained.
Abstract: After treatment of two varieties of Brassica campestris L (2n=20), T10 and T151 with radioactive chemicals P32 and S35, having different concentrations, aberrant cells, for studying the effects were scored in meiosisAccording to the nature of abnormalities in metaphase and early anaphase cytological effects and origin of different abnormal configurations were explainedSignificance of probability of nature of abnormalities was estimated by X2 test and estimate of aberration rates were based on p=n-n/N and SE=√p(1-p/n) was also considered as proportion abnormalities to the total confidence limits Sampling error was also calculated per treatment in percent to record optimum sample size for analysisLinearship between treatments and cytological aberrations was shown

Journal ArticleDOI
TL;DR: Exposure of human leukocytes in vitro to concentrations of chloridazepoxide hydrochloride for varying periods of time failed to demonstrate any increase in incidence of chromosome breakage, gaps, or abnormal forms when compared to control cultures.

Journal ArticleDOI
TL;DR: Infection of mouse, rat, hamster, or chicken cells with adenovirus types 5 and 12 or SV40 caused inhibition of subsequent challenge with VSV, EMC and vaccinia viruses, and after transformation with SV40, mouse cells showed increased VSV sensitivity in distinction to acutely infected cells in which the challenge virus was inhibited.
Abstract: Infection of mouse, rat, hamster, or chicken cells with adenovirus types 5 and 12, or SV40, caused inhibition of subsequent challenge with VSV, EMC and vaccinia viruses. This effect was most marked with adenovirus on mouse cells, where a transitory phase of stimulation was frequently demonstrated immediately after adenovirus infection. The inhibitory phase usually commenced 2–6 hours after infection and depended on infection with intact virions, although the intact adenovirus genome was not necessary. Binding of virus by antiserum did not prevent the inhibition, and inhibition could not be explained by differences in adsorption, interferon production, chromosome breakage, or the effect of soluble capsid antigens. After transformation with SV40, mouse cells showed increased VSV sensitivity in distinction to acutely infected cells in which the challenge virus was inhibited. The implications of these studies in the evolution of the transformation process are discussed.