PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “RADIATION GENETICS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2002

Bone tumorigenesis induced by alpha-particle radiation: mapping of genetic loci influencing predisposition in mice.

The present study was carried out to determine the extent to which genetic factors modify the incidence of radiation-induced bone tumorigenesis in mice, and to map putative susceptibility genes. We conducted a genome-wide linkage analysis in a cohort of 47 interstrain backcrossed mice. After the mice were injected with the bone-seeking alpha-particle-emitting radionuclide (227)Th, 21 of the mice developed osteosarcomas. Two loci, one on chromosome 7 close to D7Mit145 and a second on chromosome 14 (D14Mit125), exhibited suggestive linkage to osteosarcoma predisposition, with LOD scores of 1.37 and 1.05, respectively. The LOD score increased considerably when interaction between these two loci was taken into account (LOD = 3.48). Nine of 12 mice inheriting a susceptibility allele at both loci developed osteosarcomas after (227)Th injection, compared to only four osteosarcomas in 18 animals that did not inherit either of the susceptibility alleles. Variance component analysis revealed that these genetic factors determine approximately one-fifth of the total incidence of osteosarcomas. This study demonstrates the presence of a genetic component that modulates predisposition to radiation-induced osteosarcoma.

Aging↗
PubMed2001

A high-resolution consensus linkage map of the rat, integrating radiation hybrid and genetic maps.

We have constructed a high-resolution consensus genetic map of the rat in a single large intercross, which integrates 747 framework markers and 687 positions of our whole-genome radiation hybrid (RH) map of the rat. We selected 136 new gene markers from the GenBank database and assigned them either genetically or physically to rat chromosomes to evaluate the accuracy of the integrated linkage-RH maps in the localization of new markers and to enrich existing comparative mapping data. These markers and 631 D-Got- markers, which are physically mapped but still uncharacterized for evidence of polymorphism, were tested for allele variations in a panel of 16 rat strains commonly used in genetic studies. The consensus linkage map constructed in the GK x BN cross now comprises 1620 markers of various origins, defining 840 resolved genetic positions with an average spacing of 2.2 cM between adjacent loci, and includes 407 gene markers. This whole-genome genetic map will contribute to the advancement of genetic studies in the rat by incorporating gene/EST maps, physical mapping information, and sequence data generated in rat and other mammalian species into genetic intervals harboring disease susceptibility loci identified in rat models of human genetic disorders.

Animals↗
PubMed1985

DNA-mediated gene transfer efficiency is enhanced by ionizing and ultraviolet irradiation of rodent cells in vitro. I. Kinetics of enhancement.

The enhancement effects of ionizing and ultraviolet radiation on the efficiency of DNA-mediated gene transfer were studied. The established cell line, Rat-2, consists of cells that are density-dependent contact-inhibited and produce flat monolayers in vitro. When these cells are infected with SV40 virus, a small fraction of cells becomes morphologically "transformed" due to the stable expression of the viral A-gene. Rat-2 cells are competent for DNA-mediated gene transfer, deficient in thymidine kinase activity (TK-), and will die in HAT selective media. Confluent Rat-2 cells were transfected with purified SV40 viral DNA (via calcium phosphate precipitation), irradiated with either X rays or ultraviolet, trypsinized, plated, and assayed for the formation of foci on Rat-2 monolayers. Both ionizing and ultraviolet radiation enhanced the frequency of A-gene transformants/survivor compared to unirradiated transfected cells. These enhancements were nonlinear and dose dependent. A recombinant plasmid, pOT-TK5, was constructed that contained the SV40 virus A-gene and the Herpes Simplex virus (HSV) thymidine kinase (TK) gene. Confluent Rat-2 cells transfected with pOT-TK5 DNA and then immediately irradiated with either X rays or 330 MeV/amu argon particles at the Berkeley BEVALAC showed a higher frequency of HAT+ colonies/survivor than unirradiated transfected cells. In both cases the enhancement contained a linear and a higher order component in dose, but the argon ions were at least twice more efficient than X rays in producing enhancement per unit dose. Rat-2 cells transfected with pOT-TK5, X-irradiated, and assayed for either TK transformation or A-gene transformation showed the same dose dependence for radiation enhancement. Rat-2 cells transfected with the plasmid, pTK2, containing only the HSV TK-gene were enhanced for TK transformation by both X rays and ultraviolet radiation. SV40 A-gene products are not necessary for the radiation enhancement of the efficiency of gene transfer. This in vitro system will be used to study the lesions produced by ionizing radiation on mammalian cell DNA that may act as substrates for integration of exogenously introduced plasmid DNA.

Animals↗
PubMed2001

Retrospective biological dosimetry of absorbed radiation.

Frequencies of chromosomal translocations in human peripheral blood lymphocytes irradiated in vitro by 200 kV X rays have been estimated by the fluorescence in situ hybridisation (FISH) technique. Probes specific for whole chromosomes 1, 3 and 4 were labelled with, biotin 16 dUTP + digoxigenin 11 dUTP; biotin 16 dUTP and digoxigenin 11 dUTP respectively, to achieve three colour FISH to distinguish exchanges involving individual chromosomes. The translocation frequencies for individual chromosomes suggested a relationship between the response and the genomic content of the chromosomes studied. Dose-response curves derived from translocations involving all the three painted chromosomes (22.3% of the genome) showed a linear-quadratic response with alpha and beta coefficients of 0.027 +/- 0.009 Gy-1 and 0.033 +/- 0.004 Gy-2, corresponding coefficients for the response curves extrapolated to the entire genome are 0.072 +/- 0.026 Gy-1 and 0.075 +/- 0.011 Gy-2 respectively. Dose-response curves for the induction of dicentrics involving painted chromosomes also showed a similar response, but the dicentric frequencies were consistently lower than the translocation frequencies for all the doses studied. Dose fractionation resulted in a small but significant reduction in the yield of exchanges, thus suggesting repair of some radiation damage during the period between the two fractions. Retrospective biological dosimetry was attempted with FISH assay of five radiation workers with chronically accumulated doses of approximately 500 mSv received over a period of 2-3 decades. Among the 2421 metaphases scored in these subjects 28 translocations involving the painted chromosomes were detected. The dose estimates based on FISH assay ranged from 0.215 +/- 0.116 Gy to 0.635 +/- 0.292 mGy, thus suggesting the usefulness of this assay in retrospective biological dosimetry.

Adult↗
PubMed1985

Second malignant neoplasms in children: an update from the Late Effects Study Group.

This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Genomic mapping of chromosomal region 2p15-p21 (D2S378-D2S391): integration of Genemap'98 within a framework of yeast and bacterial artificial chromosomes.

The region of chromosome 2 encompassed by the polymorphic markers D2S378 (centromeric) and D2S391 (telomeric) spans an approximately 10-cM distance in cytogenetic bands 2p15-p21. This area is frequently involved in cytogenetic alterations in human cancers. It also harbors the genes for several genetic disorders, including Type I hereditary nonpolyposis colorectal cancer (HNPCC), familial male precocious puberty (FMPP), Carney complex (CNC), Doyne's honeycomb retinal dystrophy (DHRD), and one form of familial dyslexia (DYX-3). Only a handful of known genes have been mapped to 2p16. These include MSH2, which is responsible for HNPCC, FSHR, the gene responsible for FMPP, EFEMP-1, the gene mutated in DHRD, GTBP, a DNA repair gene, and SPTBN1, nonerythryocytic beta-spectrin. The genes for CNC and DYX-3 remain unknown, due to lack of a contig of this region and its underrepresentation in the existing maps. This report presents a yeast- and bacterial-artificial chromosome (YAC and BAC, respectively) resource for the construction of a sequence-ready map of 2p15-p21 between the markers D2S378 and D2S391 at the centromeric and telomeric ends, respectively. The recently published Genemap'98 lists 146 expressed sequence tags (ESTs) in this region; we have used our YAC-BAC map to place each of these ESTs within a framework of 40 known and 3 newly cloned polymorphic markers and 37 new sequence-tagged sites. This map provides an integration of genetic, radiation hybrid, and physical mapping information for the region corresponding to cytogenetic bands 2p15-p21 and is expected to facilitate the identification of disease genes from the area.

Chromosome Mapping↗
PubMed1996

Mammalian X ray sensitive mutants: a tool for the elucidation of the cellular response to ionizing radiation.

The complexity of the cellular response to ionizing radiation is indicated by many complementation groups identified among mammalian cells sensitive to ionizing radiation. Genetic complementation analysis of these mutants has been based on cell fusion and complementation of cell killing by X ray, whereas complementation of RDS after gamma rays has led to false results among AT cell lines and could not also be used in rodent cells. Studies on the relationship between cell killing and RDS following gamma irradiation have indicated that (a) RDS is not responsible for cell killing and (b) DNA replication in response to gamma rays is controlled by several genes. Complementation groups established in rodent cell mutants have led to the identification of the gene function in several mutants, and remarkable progress has been made in the understanding of DSB repair and its involvement in V(D)J recombination. The remaining complementation groups of X ray sensitive mutants await the determination of the role of the defective genes in the pathways operating in mammalian cells against ionizing radiation. One group of rodent mutants seems to be defective in the gene homologous to the ATM gene, and so far no more human counterparts have been found among rodent mutants. Newly characterized mutants, V-C8 and UV40, showed combined features of several human disorders, suggesting that their defective gene products could be involved in several pathways handling the response to DNA damage.

Animals↗
PubMedDate not supplied

[Interactions of inhibitor of free radical reactions and 2-deoxyribosyl macroradicals].

By steric computer modelling of five types of 2-deoxyribosyl radicals and their molecular products generated in DNA by radiation as a result of R + InH = RH + In reaction the displacement of DNA bases (maximum--for C'1 atoms and minimum for C'3 ones) has been determined. Literature data on the DNA decay in the irradiated cells, and in DNA frozen solutions as well as the data on radiolysis of compounds modelling separate DNA fragments allowed to offer a general scheme of the every 2-deoxyribosyl radical transformation and to calculate a balance between the intermediate and final molecular products (processes) of the 2-deoxyribosyl radiolysis. The DNA conformation change due to the 2-deoxyribosyl stereoisomers formation at C'3 and C'4 atoms is discussed as one of the suggested reasons for genetic radiation mutation.

Adenine↗
PubMedDate not supplied

[Restoration of pine plantations after effect of ionizing radiation in the region of the accident at the Chernobyl Atomic Energy Station].

The main results of the 12-year radiation-genetic monitoring of radiobiological, cytogenetic, and genetic parameters in the Pinus sylvestris L. forest plantations from the zone of the accident at the Chernobyl nuclear power plant presented. Acute ionizing irradiation at doses > 1 Gy was shown to induce the formation of morphoses and depressed growth; at doses > 2 Gy, the reproductive ability of the trees declined. The radiobiological parameters showed a linear (or close to linear) dose-effect relationship. Acute irradiation at a dose of 0.5 Gy induced cytogenetic and genetic effects that were significantly higher than the corresponding control values. The relationship between the cytogenetic effects and the absorbed dose was exponential. The dependence of the mutation frequency at specific loci on the absorbed dose was described by a nonlinear curve. The results of cytogenetic analysis of sprouts obtained from seeds annually (1986-1998) collected in zones of slight, moderate, and strong damage of Pinus sylvestris L. are presented.

Chromosome Aberrations↗
PubMed1983

Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. XVI. Adaptation to the mutagenic effects of X-rays in several experimental populations with irradiation histories.

Selection responses of the laboratory stock Berlin wild (+60, +K) of Drosophila melanogaster to the mutagenic effects of high, accumulated exposures of X-rays were studied in several sub-populations with long irradiation histories. Interest was focussed on adaptive adjustments of mutation rates. In samples from the populations, radiosensitivities of immature oocytes were tested, by using dominant lethals (A), X-chromosome losses (B) and sex-linked recessive lethals (C) as end-points of genetic radiation damage. Populations RO II and RO V are similar to the previously studied population RO I and were exposed to 2100 R/generation, delivered to oocyte stages 6-14, mature sperm, and spermatids. RO II (first tests after 160 generations) is radioresistant relative to +60 (control). The resistance was characterized by dose-reduction factors (DRFs) of 1.72 (with respect to end-points A, B) and 1.53 (C), and these were similar to those previously obtained for RO I. The resistance of RO II was inherited semidominantly as was that of RO I, and the radiosensitivity of the hybrids RO I/RO II was similar to that of RO I and RO II with respect to end-points A and B. RO V did not become resistant within 25 generations of irradiation history (A). Populations RO III (6000 R/generation) and RO IV (7000 R/generation) have histories of irradiations given to oogonia and spermatogonia. Radiosensitivities of immature oocytes of RO III did not differ from those of +K after 55 generations, but after 105 and 135 generations of irradiation history, DRFs of 1.2 (A) and 1.44 (B) were observed. RO IV was characterized in generations 55-135 by DRFs of 1.31 (A) and 1.72 (B). Selection for relative radioresistance of immature oocytes was found (1) to be reproducible (RO II-RO IV), (2) not to require genetic pre-adaptation (RO V), and (3) to be, in part, also achieved by 'indirect' selection (RO III, RO IV). It is concluded that mutation rates in populations are selectively adjusted to evolutionary requirements.

Animals↗
PubMed1985

Electrophoretic variants of blood proteins in Japanese. IV. Prevalence and enzymologic characteristics of glucose-6-phosphate dehydrogenase variants in Hiroshima and Nagasaki.

Electrophoretic screening of glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PD) was conducted one sample of 9,260 children born to the atomic bomb survivors in Hiroshima (Honshu) and Nagasaki (Kyushu). The prevalence of electrophoretic variants was 0.11% in males and 0.42% in females in Hiroshima, and 0.16% in males and 0.31% in females in Nagasaki. Enzymologic characteristics of 10 variants obtained from three males and seven hemizygous fathers of heterozygous females were examined. As a result, three new types of G6PD variants were identified among five variants detected in Hiroshima, and three new types among five variants in Nagasaki. All the variants except one belonged to Class 3, as defined by Yoshida et al. (1971).

Adolescent↗