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Biomedical subjects

B K Vig

Publications and source records attributed to B K Vig.

At least 73 records · Page 4Linked to original sources
PubMed1982

Sequence of centromere separation: role of centromeric heterochromatin.

The late metaphase-early anaphase cells from various tissues of male Mus musculus, M. poschiavinus, M. spretus, M. castaneus, female and male Bos taurus (cattle) and female Myopus schisticolor (wood lemming) were analyzed for centromeres that showed separation into two daughter centromeres and those that did not show such separation. In all strains and species of mouse the Y chromosome is the first one to separate, as is the X or Y in the cattle. These sex chromosomes are devoid of constitutive heterochromatin, whereas all autosomes in these species carry detectable quantities. In cattle, the late replicating X chromosome appears to separate later than the active X. In the wood lemming the three pairs of autosomes with the least amount of centromeric constitutive heterochromatin separate first. These are followed by the separation of seven pairs of autosomes carrying medium amounts of constitutive heterochromatin. Five pairs of autosomes with the largest amounts of constitutive heterochromatin are the last in the sequence of separation. The sex chromosomes with medium amounts of constitutive heterochromatin around the centromere, and a very large amount of distal heterochromatin, separate among the very late ones but are not the last. These observations assign a specific role to centromeric constitutive heterochromatin and also indicate that nonproximal heterochromatin does not exert control over the sequence in which the centromeres in the genome separate. It appears that qualitative differences among various types of constitutive heterochromatin are as important as quantitative differences in controlling the separation of centromeres.

Anaphase↗
PubMed1982

Hyperthermic potentiation of chromosome aberrations by anticancer antibiotics.

In view of the success of hyperthermia as a modality in cancer treatment, we have studied its effect on chromosomes in combination with anticancer antibiotics. Three classes of chemicals, one with a non-delayed type of effect (adriamycin), one with a delayed type of effect (mitomycin C), and one with a truely radio-mimetic effect (bleomycin) were selected for study on human lymphocytes and Chinese hamster K-1 cells. Propane sultone was also included because its effect on plants is suppressed by hyperthermia. The data show increased because its effect on plants is suppressed by hyperthermia. The data show increased potential of these chemicals to induce chromosome aberrations when applied at temperatures higher than 37 degrees C, irrespective of the phase of cell cycle. The potentiation may be due to true synergism (bleomycin) of facilitation of entry of larger quantities of the drug (adriamycin). No potentiating effect was observed on the induction of sister chromatid exchanges (SCEs).

Animals↗
PubMed1981

Sequence of centromere separation: analysis of mitotic chromosomes in man.

Mitotic chromosomes from human peripheral lymphocytes studied at the junction of metaphase and anaphase show that the centromeres of various chromosomes separate in a nonrandom, apparently genetically controlled sequence. It does not depend upon the position of the centromere in the chromosome, the length of the chromosome or total amount of detectable C-chromatin. In man, several chromosomes e.g. 18, 17, 2, separate very early. Such "early" cells do not include nos. 1, 13, 14, 15, and Y and very rarely nos. 21 and 22. The last separating chromosomes are those from group D, G, no. 1, 16, and Y. The possible implication of these findings in evolution, non-disjunction and the control of centromere separation sequences is discussed.

Adult↗
PubMed1981

Sequence of centromere separation: an analysis of mitotic chromosomes from long-term cultures of Potorus cells.

The sequence of centromere separation in late metaphase/anaphase cells from a long term culture of cells from a male rat-kangaroo, Potorus tridactylus, was studied. The karyotype of the PTK-1 line has five pairs of autosomes, one modified No. 1 (M1), and X, Y1 and Y2. In 87% of the cells the centromeres of No. 4 or 5 were among the first to separate. Y1, Y2, X, or the marker, M1, were not the earliest chromosomes to separate. Y2 separated last most frequently (59%), followed by X, M1 and Y1. The overall relative averages for the sequence of separation in the entire genome (centromere separation index or CSI) are 1.52, 1.40, 1.11, 0.92, 0.88, 0.86, 0.68, 0.56, and 0.27 for 5, 4, 2, 1, Y1, 3, M1, X, and Y2, respectively (the average for the whole genome is 1). The data indicate that the centromeres of the chromosomes of potorus separate in a specific, genetically controlled, non-random sequence. The chromosomes separating late have larger amounts of centromeric heterochromatin; all of this or part of it may be the controlling element for the sequence of separation.

Animals↗
PubMed1979

Hyperthermic enhancement of chromosome damage and lack of effect on sister-chromatid exchanges induced by bleomycin in Chinese hamster cells in vitro.

Chinese hamster cells, M-3, were treated with BLM (1--4 micrograms/ml) for 30 min to 1 h at 37 degrees or 43 degrees C. After treatment, the cells were reincubated at 37 degrees until recovery. The material treated at 43 degrees showed increased damage expressed as chromosome and chromatid-type breaks and exchanges. Since the amount of BLM entering the cell at 37 degrees is supposedly similar to that which enters the cell at 43 degrees, the enhanced damage is the result of true synergism, and not the facilitation of the drug's entry into the cell.

Animals↗
PubMed1978

Mutagenic and chromosome-breaking effects of azide in barley and human leukocytes.

Azide (10-3 M, solution buffered at pH 3) is more effective in inducing mutations in embryonic shoots of seeds germinated between 8 and 16 h than in non-germinated seeds and in seeds germinated between 0 and 8 h and 16 to 28 h. This peak of chlorophyll-deficient seedling mutation frequency coincides with maximum frequencies of seeding lethals and DNA replication in the cells of the embryonic shoot. The mutation data suggest azide may only act on replicating DNA. Azide induced no chromosome-aberration frequencies significantly above controls in (1) embryonic shoots of barley seeds germinated for 8--12 h, (2) microspores of barley and (3) human leukocytes. It appears to be a point-mutation mutagen.

Azides↗
PubMed1978

Somatic crossing-over in Glycine max (L.) merrill: activation of dimethyl nitrosoamine by plant seed and comparison with methyl nitrosourea in inducing somatic mosaicism.

The soybean system used for detecting environmental mutagens is analyzed for various types of spots on the leaves of heterozygous y11y11 plants and homozygous y11y11's induced by a nitrosoamine (dimethyl nitrosoamine, DMN) and a nitrosoamide (methyl nitrosourea, MNU). It is shown that the nitrosoamine can be "activated" by the seed (is converted to a true mutagen) without the addition of NADPH or S-9 fraction of the liver homogenate as is necessary in animal tissue culture or bacterial studies. Whereas somatic mosaicism in soybean can be induced with a dose as low as 1.25 ppm of DMN, the upper limit in spot production is reached at around 60 ppm concentration, applied for 0--24 h. Such saturation effect may be due to a limited amount of DMN being converted to true mutagen. MNU, on the other hand, does not show such limitations, perhaps because of its property of being a direct mutagen not necessitating an intermediate step required for converting the promutagen DMN. The frequency of twin spots on Y11y11 leaves increases only slightly by either DMN or MNU, suggesting only a small increase in somatic crossing-over induced by the two chemicals. The yellow spots increase the most, perhaps due to segmental losses carrying Y11 or non-complementary segregation of exchanges involving non-homologous chromosomes. Neither chemical is found capable of mutating y11 to Y11 as seen by the general lack of light green sectors on y11Y11 plants. Usefulness of the soybean system in studying mutagenesis is briefly discussed.

Crossing Over, Genetic↗
PubMed1978

Genetic toxicology of bleomycin.

Bleomycin (BLM), an antibiotic obtained from Streptomyces verticillus, is of significance as an antineoplastic agent. The compound is actually the mixture of some 200 related forms which differ from each other in the amine moiety. The drug, at low concentrations, can cause elimination of bases, particularly thymine. This causes strand breakage of DNA and inhibition of cell growth. The influence of BLM on cell growth may be unrelated to the effects on DNA. In general, mitotically dividing cells show more DNA damage than non-dividing cells. G2 seems to be the most sensitive phase indicating that cell death may not be related to a direct effect of BLM on DNA replication. The antibiotic shows specific effects on chromatin and causes chromosomal damage in all sub-phases of interphase. It can affect early prophase chromosomes also. Suggestion has been made that BLM-induced breakage and cell death are similar to those induced by densely ionizing radiations. Whereas the antibiotic affects the frequency of somatic crossing over and produces micronuclei, the data on mutation induction and production of sister-chromatid exchanges do not permit classifying BLM as a potent inducer of these phenomena. The genetic effects of BLM can be modified quantitatively by thiol compounds, caffeine, hyperthermia and H2O2. It is concluded that the available data do not permit assessment of genetic damage in the offsprings of BLM-treated patients. Such studies are urgently needed, as are the studies to find out the effects of BLM on meiotic phenomena.

Animals↗
PubMed1978

Somatic mosaicism in plants with special reference to somatic crossing over.

Plant systems in use for the detection of environmental mutagens appear capable of detecting all types of genetic effects which can be studied in animals. The study of somatic mosaicism, however, is better developed in plants than in higher animals. A case is presented here which shows the ability of plant systems in analyzing a host of genetic end points, including chromosome aberrations like deletions, somatic crossing over, numerical inequality, gene conversion, paramutations and point mutations. The systems in general use utilize certain varieties of Tradescantia, Glycine max, Nicotiana tabacum, Antirrhinum majus, Petunia hybrida, and Arabidopsis thaliana. Heterozygous plants or their homozygous counterparts with gene markers affecting chlorophyll development or anthocyanin in floral parts are exploited in these studies. Mutagens produce different frequencies of different types of spots typical of the mode of action of the agent. Analysis of these parameters may be used to predict, at least qualitatively, the kind of genetic damage that might be produced in man. Besides, one can test the validity of interpretation by traditional progeny tests of plants raised from tissue culture from sectors as in Nicotiana and/or by precursor analysis as done in Antirrhinum. The study of mosaicism in plants offers quite inexpensive, rapid, and reliable tests of mutagenicity at least as a preliminary eukaryotic test system.

Biotransformation↗
PubMed1978

Effect of hypothermia and hyperthermia on the induction of chromosome aberrations by adriamycin in human leukocytes.

When human leukocytes are treated with adriamycin (ADR) for brief durations of 1 to 2 hr at concentrations ranging between 0.04 and 0.25 microgram/ml, a dramatic reduction is observed in the frequency of chromosome aberrations in cells treated at 4 degrees in comparison to those treated at 37 degrees. Conversely, a severalfold increase in the frequency of aberrations is found if temperature at the time of ADR treatment is raised to 43 degrees. At higher temperatures, the most dramatic increase is in the frequency of exchanges. These results point to a parallelism between these studies and those carried out previously for determining cell death with hyperthermia and ADR treatment. This effect on chromosome aberrations appears only if temperatures of 4 of 43 degrees are applied during the period of exposure of cells to ADR. No effect is evident if cells are posttreated at 4 or 43 degrees after ADR is removed from the medium. The question of true synergism versus "facilitation" of influx of ADR into cells is discussed in light of the information obtained by other workers on total quantities of the drug present in the cell.

Cell Survival↗
PubMed1977

Study on cytological effects of carofur -- a new mutagen.

Chinese hamster cells (line V-79) and human leukocytes in vitro and mice of the CBA strain were treated with carofur (also called nifurprazinum), an antibacterial agent of pharmaceutical importance. At concentrations as low as 20 ppm, the in vitro treatments of cells of Chinese hamster and human lymphocytes expressed chromosome aberrations, almost exclusively of deletion type. This effect resembles that of fluorodeoxyuridine but may not necessarily reflect the same basic mechanism involved. When Chinese hamster cells were treated with 5 ppm or more of carofur for 24 hr, a 3-fold increase in the frequency of somatic sister chromatid exchanges was observed. An interesting phenomenon of "centromeric association" was observed in the bone marrow cells of mice treated with carofur, where the centromeres of the acrocentric chromosomes were oriented towards each other in groups of 2's or more.

Animals↗
PubMed1976

Sequence of centromere separation of mitotic chromosomes in Chinese hamster.

Chromosome preparation in late metaphase cells from bone marrow of colcemid treated male Chinese hamsters were used to analyse the sequence of separation of sister centromeres. Chromatids of chromosomes 2 and 1 are the first ones to separate at centromeres, followed by members of group B, D and C. Some acrocentric chromosome is always the last one to separate at the centromere. The data point to a possible correlation between the position of a centromere in the separation sequence in the genome and the amount of centromeric heterochromatin as well as relation to the phenomenon of non-disjunction.

Animals↗
PubMed1975

Mutagen specificity in the induction of mitotic crossing-over in Saccharomyces cerevisiae.

A diploid yeast strain, D81, was constructed heterozygous for seven recessive markers linked on the left arm of chromosome VII to study the localization of induced mitotic crossing over. The mutagens used were carofur also called nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylene hydrochloride), diepoxybutane, ethylmethanesulfonate, nitrous acid and 1-nitrosoimidazolidinone-2. All agents induced high frequencies of mitotic crossing over at doses exerting only a low degree of killing. The distribution of recombinational events was compared for five intervals. The distribution pattern of spontaneous mitotic crossing over was different from all the patterns obtained after mutagenic treatments. Nitrous acid and diepoxybutane induced the same pattern, which was different from the patterns induced by carofur, EMS and 1-nitrosoimidazolidinone-2. The patterns induced by the latter three mutagens were again different amongst each other. Repeat experiments showed that the patterns induced by a given mutagen were reproducible. Tetrad analysis with a representative sample of segregants induced by diepoxybutane and carofur showed that the treatments actually induced mitotic crossing-over. The pattern of meiotic recombinational events was different from those of spontaneous and mutagen induced mitotic recombination. Inducibility of mitotic crossing-over was low at the proximal and distal ends of the chromosome arm and highest in the middle. Each interval showed a different response to those mutagens that differed in their patterns of induced mitotic crossing over. The observed mutagen specific effects are considered as an indication of mutagen specificity. No plausible explanation for mutagen specificity could be given. However, the data presented reveal the same situation as found in induction of chromosome breaks, as reported by other authors. Apparently, mutagen specificity is quite a general phenomenon even for genetic effects in larger intervals of a chromosome.

Chromosome Mapping↗