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At least 811 records · Page 45Linked to original sources
PubMed2000

Genetic susceptibility to radiations. Which impact on medical practice?

Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiation. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiation for better treatment of their malignant tumors. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of this new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiation. Then the main tests capable of detecting in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for this specific subset of patients suffering from a genetic disorder with a susceptibility to radiations.

Genetic Predisposition to Disease↗
PubMed2000

Differences between the radiation hybrid and genetic linkage maps of bovine chromosome 5 resolved with a quasi-phylogenetic method of analysis.

Two major differences were detected in gene order between the radiation hybrid map and the genetic linkage map of bovine Chromosome (Chr) 5, and these were resolved by analyzing the raw radiation hybrid data by a quasi-phylogenetic method. Seventeen loci were typed on the new cattle whole genome radiation hybrid panel. Most of these loci are framework loci and include AGLA293, BM315, BM6026, BP1, BZRP, CD9, CSSM22, CSSM34, CYP2D@, ETH2, ETH10, ETH152, IGF1, LALBA, SLC2A3, SYT1, and TPI1. BP1 was found to be closer to the centromere than either BM6026 or SYT1 with two standard computer software packages for analyzing radiation hybrid panel data. This is inconsistent with any of the genetic linkage maps as well as their consensus. CYP2D@ was placed between ETH2 and BZRP, and this is also inconsistent with the genetic linkage maps, since CYP2D@ should be the most telomeric of the loci tested in this study. Resolution was reached by analyzing the raw radiation hybrid data for clones that bind some but not all of the loci, and the binding pattern was more consistent with the linkage maps and less consistent with the software-generated radiation hybrid map. The comparative mapping data confirm the relative inversion of gene order of SYT1 compared with humans and mice. A non-polymorphic fragment for CD9 indicates the conservation of gene order for three loci located on human Chr 12p. The genes of bovine Chr 5 conserved on human Chr 12p are located separately from the genes conserved on human Chr 12q. It is recommended that the raw data for radiation hybrid maps be made publicly available so that conflicts in gene order can be evaluated explicity.

Animals↗
PubMed2000

Radiation physics and genetic targeting: new directions for radiotherapy. The Douglas Lea Lecture 1999.

Radiation as a cancer treatment modality is of high physical precision but limited biological specificity. Targeted radiotherapy, the delivery of radiation to cancer cells by radioisotopes conjugated to tumour-seeking targeting agents, is a biologically attractive option but is currently effective for just a few tumour types (neuroblastoma, lymphoma) for which efficacious targeting agents are available. Radiobiological modelling and radiation microdosimetry have provided useful guidelines in choosing treatment strategies for targeted radiotherapy. These considerations generally favour the incorporation of targeted radiotherapy as one component of a multimodal treatment regimen. Very recently, gene therapy techniques have been developed which should enhance the clinical efficacy of both external beam radiation and targeted radiotherapy. Typically, non-harmful viruses are modified to incorporate therapeutic genes which cause altered cellular radiosensitivity or which facilitate the cellular uptake of targeting agents. To achieve specificity, therapeutic genes would be co-transfected with tissue-specific promoter genes causing the therapeutic genes to be expressed in cells of particular types. In laboratory models, our research group are exploring the transfection-mediated uptake of the targeting agents MIBG and sodium iodide. These approaches do not require transfection of every cell in order to cure a tumour-cells which have escaped transfection may be sterilized by radiation cross-fire from transfected neighbours. A new task for radiation microdosimetry is to quantify the cross-fire effect and to compute the efficacies of gene transfection which will be required for tumour cure. In the spirit of Douglas Lea, the analytic approach of physics can be used to illuminate and enhance developments in genetics, to the benefit of medicine.

3-Iodobenzylguanidine↗
PubMed2002

Mechanistic and genetic studies of radiation tumorigenesis in the mouse--implications for low dose risk estimation.

Radiation cancer risk estimates remain firmly based upon epidemiological data. Experimental validation of the fundamental aspects of these risk estimates relies on animal studies. In particular, animal model systems for radiation carcinogenesis can provide data for mechanistic modelling approaches to risk estimation. The accuracy and validity of risk estimation models developed will depend upon the extent of our understanding of the process of radiation carcinogenesis. The study of 'spontaneous' tumours in humans continues to provide a sound context in which to consider the mechanisms of radiation carcinogenesis. Several mouse radiation carcinogenesis systems are considered here with particular reference to the nature of the initiating event and the influence of genetic susceptibility on radiation-induced cancer.

Acute Disease↗
PubMed2006

Genetic effects of radiation in atomic-bomb survivors and their children: past, present and future.

Genetic studies in the offspring of atomic bomb survivors have been conducted since 1948 at the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Past studies include analysis of birth defects (untoward pregnancy outcome; namely, malformation, stillbirth, and perinatal death), chromosome aberrations, alterations of plasma and erythrocyte proteins as well as epidemiologic study on mortality (any cause) and cancer incidence (the latter study is still ongoing). There is, thus far, no indication of genetic effects in the offspring of survivors. Recently, the development of molecular biological techniques and human genome sequence databases made it possible to analyze DNA from parents and their offspring (trio-analysis). In addition, a clinical program is underway to establish the frequency of adult-onset multi-factorial diseases (diabetes mellitus, high blood pressure, and cardiovascular disease etc) in the offspring. The complementary kinds of data that will emerge from this three-pronged approach (clinical, epidemiologic, and molecular aspects) promise to shed light on health effects in the offspring of radiation-exposed people.

Abnormalities, Radiation-Induced↗
PubMed1999

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗
PubMed1994

[Analysis of dominant and recessive sex-linked lethal mutations induced by low radiation doses in genetically different strains of Drosophila melanogaster w and MS].

Frequencies of induced recessive sex-linked lethal mutations (RSLLM) and dominant lethal mutations (DLM) were analyzed in genetically different Drosophila melanogaster strains w and ms after their exposure to radiation on radioactive soil in laboratory conditions. The RSLLM test applied to males after their 14-day radiation exposure yielded controversial results. An analysis of induced and spontaneous DLM demonstrated an increase in the frequency of early embryonic lethal mutations in the experiment (radiation exposure) in comparison with the control (spontaneous mutation rate) in both strains examined.

Animals↗
PubMed1991

Genetic analysis of ionising radiation sensitive mutants of cultured mammalian cell lines.

The genetic diversity of a range of ionising radiation sensitive mutants of cultured mammalian cell lines has been examined. Hybrids were constructed from suitably marked diploid cells by cell fusion and selected using resistance to HAT and ouabain. Hybrids were examined for ploidy and gamma-ray sensitivity. The data suggest that at least 8 and possibly 9 complementation groups exist which confer sensitivity to ionising radiation. Mutants in at least 3 distinct complementation groups have a reduced ability to rejoin DNA double-strand breaks.

Animals↗
PubMed1978

The effect of ultrasound and its combination with radiation on the genetic material of Saccharomyces cerevisiae.

Ultrasonication at 20 kHz, intensity 35 W/cm2 and amplitude 15--25 micron of a diploid strain of Saccharomyces cerevisiae was found to act as a weak mutagen with maximum efficiency at the 20% survival of the cells. Under these conditions, the frequency of reversion of the suppressible allel ilv1-92 increased ten times, the frequency of mitotic gene conversion four times. Doses leading to survivals lower than 20% led to a slight increase in the frequency of cytoplasmic respiration-deficient mutants. Submutagenic doses applied immediately after gammaradiation or UV light did not substantially increase the effect of these physical agents on the genetic material of the yeast strain investigated. Application of ultrasound prior to UV radiation did not considerably influence the effect of the radiation either.

Gamma Rays↗
PubMed2003

Optimization and implementation of piezoelectric radiators using the genetic algorithm.

Very thin and small (45 mm x 35 mm x 0.35 mm) piezoelectric radiators have been developed in this research. The system is modeled by using the energy method in conjunction with the assumed-modes method. Electrical system, mechanical system, and acoustic loading have all been accounted for during the modeling stage. On the basis of the simulation model, the genetic algorithm (GA) is employed to optimize the overall configurations for a low resonance frequency and a large gain. The resulting designs are then implemented and evaluated experimentally. Performance indices for the experimental evaluation include the frequency response, the directional response, the sensitivity, and the efficiency. It is found in the experimental results that the piezoelectric radiators are able to produce comparable acoustical output with significantly less electrical input than the voice-coil panel speakers.

Journal Article↗