PubMed Health⌕ Search

Biomedical subjects

G Breckon

Publications and source records attributed to G Breckon.

At least 19 recordsLinked to original sources
PubMed1998

Establishment and characterization of bone marrow stroma-dependent leukemia cell line, HB-1.

Radiation-induced M361 leukemia bearing mice (M361 mice) show characteristics of acute myelogenous leukemia (AML) with granulocytosis. Granulocyte-macrophage colony forming unit (CFU-GM) increased in the bone marrow and spleen and high activity of colony stimulating factor (CSF) was found in the sera of M361 mice. A cell line (HB-1) was established from the spleen cells of M361 mice. Injection of HB-1 cells induced a similar leukemic response as M361 in syngeneic mice. HB-1 cells did not survive in the suspension culture, but proliferated when cultured on hemopoietic supportive stromal cells (MS-10). HB-1 cells appear to be strictly dependent on the hemopoietic supportive bone marrow stroma, which would provide a useful model for the study of cell-cell interactions between hemopoietic cells and marrow stromal cells.

Animals↗
PubMed1996

Chromosomal mechanisms in murine radiation acute myeloid leukaemogenesis.

Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-irradiation events in bone marrow cells in vivo and of karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2;11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore, two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal translocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis.

Acute Disease↗
PubMed1991

Murine radiation myeloid leukaemogenesis: a possible role for radiation-sensitive sites on chromosome 2.

There is a paucity of informative data on the potentially important role of specific sites of chromosomal instability in oncogenic processes. Chromosome 2 deletions and rearrangements are known to characterise radiation-induced acute myeloid leukaemia in the mouse. Here we statistically establish a concordance between chromosome 2 breakpoint clusters in these leukaemias and chromosome 2 rearrangements carried at a high in vivo frequency by progeny of irradiated haemopoietic cells. Mechanisms of radiation myeloid leukaemogenesis are discussed with respect to multiple radiation-sensitive sites encoded on chromosome 2 and the possible influence of genomic imprinting on inductive processes.

Alpha Particles↗
PubMed1991

DNA methylation changes in the IL-1 (2F) chromosomal region of some radiation-induced acute myeloid leukaemias carrying chromosome 2 rearrangements.

Acute myeloid leukaemias (AML) arising in irradiated CBA/H mice frequently have breakpoints in the F region of chromosome 2. The closely linked cytokine genes interleukin (IL)-1 alpha and beta map to this region, and the beta gene is deregulated in some AMLs. Using pulsed-field gel electrophoresis techniques, we show here that an 800 kb 2F region encoding IL-1 alpha and beta is not obviously rearranged in six leukaemias carrying chromosome 2 abnormalities. However, changes in IL-1 region DNA methylation in three leukaemias may be consistent with loss of hypermethylated sequences from one chromosome copy. These possible 2F region losses are discussed in relation to genomic imprinting and its potential role in murine myeloid leukaemogenesis.

Acute Disease↗
PubMed1990

An XXY mouse, the result of a rearrangement between one X and a Y chromosome.

A male mouse with irregular white spotting, typical of piebald, s, arose during an experiment designed to search for mutations induced in spermatogonial cells by ethylnitrosourea (ENU). On being examined cytologically it was found to carry 40 chromosomes but was effectively XXY since one of the two X chromosomes present was distally fused to a Y chromosome. In common with the previously described XXY mice, all of which carried 41 chromosomes, the mouse was sterile with a total absence of germ cells. Because of this, it was not possible to determine if the white spotting was inherited. The spotting could not be related to any observable abnormality of chromosomes known to carry spotting genes, nor could it be linked in any way with the X and Y fusion. It was concluded from the cytological considerations and the time interval (6 months) that had elapsed between mutagen treatment and birth of the offspring, that whereas the spotting was probably the result of ENU damage in a spermatogonial stem cell, the XY fusion was probably a later and spontaneous event.

Animals↗
PubMed1989

Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: a candidate initiating event for murine radiation-myeloid leukemogenesis?

The incidence of acute myeloid leukemia (AML) in CBA/H mice following exposure to single acute doses of ionizing radiation has previously been determined. A high proportion of these AMLs are characterized by rearrangement of murine chromosome 2 in the C2 and/or E5-F regions, and there is evidence that these events are a direct consequence of radiation damage to multipotential hemopoietic cells. Using a combination of in situ chromosome hybridization and mRNA analyses, we show that the cytokine gene interleukin-1 beta (IL-1 beta) is encoded in the chromosome 2 F region and is translocated in a chromosome 2---2 rearrangement in an x-ray-induced AML (N36). Also, IL-1 beta is specifically deregulated in N36 and in two other chromosome 2-rearranged AMLs but not in a fourth, which has two cytogenetically normal chromosome 2 copies. We suggest that radiation-induced specific chromosome 2 rearrangement associated with IL-1 beta deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells.

Animals↗
PubMed1989

Transmission of three radiation-induced translations in the Syrian hamster. I. Chromosome studies of male meiosis: pachytene to metaphase II.

Chromosome behaviour during meiosis in male Syrian hamsters heterozygous for one of three translocations was analysed as part of a study of the transmission of these structural changes. Synapsis was studied using preparations of synaptonemal complexes, and chiasmate associations and the results of anaphase I segregation were studied in air-dried preparations of metaphases I and II respectively. The main findings were: (i) that, at least in the two trivalent-forming translocations, there is no simple relationship between either the frequency or the extent of synapsis and chiasma formation between the chromosomes involved in the translocation; (ii) that the presence of a univalent in a substantial proportion of metaphase I cells does not necessarily lead to irregular segregation as judged by analysis of metaphase IIs; and (iii) conversely, that in translocation heterozygotes in which metaphase I contains the chromosomes involved in the translocation as a quadrivalent or as two bivalents, with no univalents or trivalents, unexpected numerical segregation can be found. The observations of meiotic chromosomes behaviour reported here show that it is not always possible to predict the effects of structural change, or to determine the basis of these effects, from an analysis of any stage of meiosis taken in isolation, or from an analysis of an apparently similar change.

Animals↗
PubMed1989

Chromosomal localization of murine interleukin-1 alpha and beta genes.

DNA analyses of mouse X Chinese hamster somatic cell hybrids and of recombinant inbred mouse strains have previously shown that the interleukin-1 alpha and beta genes are tightly linked on murine chromosome 2, approximately 4.7 cM distal to beta-2-microglobulin. In this study, using in situ chromosome hybridization, we show that the two interleukin-1 genes are located in the F region of murine chromosome 2 and discuss this physical map position in relation to conserved genetic linkage groups.

Animals↗
PubMed1989

The cytological and histological effects of photoperiodism and X-irradiation on the testes of the Syrian hamster.

The radiosensitivity of meiotic stem cells from photoregressed testes of the Syrian hamster was studied after in vivo irradiation with 2.67 Gy (1.77 Gy/min). The testes of Expt I animals were irradiated at the time of transfer from short days (11 weeks at 6L:18D (6 hours light: 18 hours) darkness) to long days (14L:10D) and sampled at weekly intervals between 5 and 10 weeks and at 15 weeks postirradiation. The Ext II animals received the same X-ray dose, 2, 4, 6, 8 weeks after the transfer to long days and were sampled 10 weeks postirradiation. In Expt I X-irradiation delayed the recovery of testis structure and function by 4 weeks. Animals in Expt II were homogeneous with regard to testicular weight, sperm count, tubule diameter and the level of pachytene, MI and MII damage. The incidence of structural chromosomal changes in primary spermatocytes at pachytene (synaptonemal complexes) and MI and MII was determined. In Exp I and II and data from X-irradiated testes (2.6 Gy) not exposed to short days (Control B, see Cawood and Breckon 1983), these cell types show a difference in sensitivity to the induction of structural damage. The lowest level of pachytene damage was in Expt II, and the ratio of the number of pachytene to MI cells showing structural change was 1.23:1 (P = 0.41), not significantly different from 1:1. In Expt I the pachytene, MI structural change ratio was 1.60:1 (P = 0.010), significantly different from 1:1. The control B ratio was 1.85:1 (P = 0.0037) which was significantly different from 1:1. The preliminary results indicate that testes fully regressed to the 'stem' cell level by exposure to short day length have a similar radiosensitivity to normal (non-regressed) testes. However, testes irradiated during the recovery phase from photoperiod-induced regression have increased sensitivity to radiation damage. The relative testis weight was reduced to a mean of 1.25 g by the sequential X-ray treatment--this may indicate that the effects of the X-rays (3 Gy) on a recovering photoregressed testis are independent of the time of the X-ray treatment during the recovery period. Recovery of tubule diameter is not perturbed and may be slightly increased, with an associated elevation of MI-MII activity--but a low spermatogonia count.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

An automated system for karyotyping mouse chromosomes.

A system developed for interactive automated analysis of human chromosomes has been modified for use with mouse cells. The system is described, with emphasis on those features that facilitate retaining for different preparations or even different species. Some performance figures are presented.

Animals↗
PubMed1988

Preliminary molecular studies on two chromosome 2 encoded genes, c-abl and beta 2M, in radiation-induced murine myeloid leukaemias.

The majority of radiation-induced murine myeloid leukaemias are characterized by deletion and/or translocation of an interstitial region of chromosome 2, and there is evidence that such events may occur very early in myeloid leukaemogenesis. Analyses presented and discussed here on the structure and function of two possibly relevant chromosome 2 encoded genes (c-abl and beta 2M) lead to the preliminary conclusion that neither are directly involved nor activationally changed by the characteristic chromosome 2 rearrangements.

Animals↗
PubMed1986

Characterisation of a new murine B cell lymphoma.

The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy.

Animals↗
PubMed1985

Induced structural changes in chromosomes of the Syrian hamster after X-irradiation of spermatogonia: comparison of dose-response curves derived from synaptonemal complexes and from air-dried preparations of metaphase I.

The dose-response relationships of the induction of structural change in chromosomes after X-irradiation of spermatogonia have been determined from analyses of synaptonemal complexes in pachytene spermatocytes and from air-dried preparations of metaphase I. The dose-response curves were superficially the same shape, with a peak yield of cells containing a multivalent at 4 Gy, although only in the pachytene data was there any statistically significant hump. The pachytene preparations were much more sensitive, revealing nearly twice the proportion of cells containing multivalents than found at metaphase.

Animals↗
PubMed1985

Chromosome aberration frequencies after partial-body irradiation of Syrian hamsters.

Graded X-ray doses up to 6.0 Gy were delivered to the rear 1/3 of body length (congruent to 1/3 body mass) of Syrian hamsters and 24 h later, peripheral blood lymphocytes were sampled, set up in culture together with bromodeoxyuridine and first post-stimulation mitotic cells were scored for chromosome-type aberrations. Very few aberrations were found at any dose and the response curve for centric exchanges ("dicentrics + centric rings") had no significant curvature or slope. Single irradiations of 3.0 Gy delivered to the whole body and sampled by identical protocol produced yields identical to, or slightly exceeding, those found for blood irradiated with the same dose in vitro. The same dose delivered to the front 2/3 or front 1/3 (head) or localised to the spleen area, and aberrations scored from blood or spleen-pulp lymphocytes, gave variable yields, but always higher than those obtained from the rear 1/3 irradiations. The results are consistent with dose-dependent interphase death of irradiated cells, coupled with a non-uniform distribution of lymphocytes within body tissues. It is estimated that some 80-90% of the lymphocytes are resident within the anterior 2/3. Detailed studies of the between-cell aberration distributions give evidence that positive selection against cells with high aberration frequencies has also occurred in these experiments.

Animals↗