Atomic Energy of Canada Limited

About: Atomic Energy of Canada Limited is a company organization based out in Ottawa, Ontario, Canada. It is known for research contribution in the topics: Zirconium alloy & Neutron. The organization has 4845 authors who have published 4826 publications receiving 102951 citations.

Defective excision repair of γ-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts

Abstract: ATAXIA telangiectasia (AT) (Louis–Bar syndrome) is a rare human neurovascular disease displaying an autosomal recessive pattern of inheritance1–3. Affected individuals, although clinically normal at birth, symptomatically develop cerebellar ataxia (loss of muscular coordination) and oculocutaneous telangiectasis (chronic dilation of the small blood vessels) in early childhood. The course of the disease follows a variable progression commonly leading to total neurological incapacitation before puberty. Accessory complications include lymphoreticular neoplasia2,3, bronchiectasis1,2, recurrent sinopulmonary infections1,2, decreased levels of serum immunoglobulins IgA and IgE (refs 3 and 4), impaired cellular immunity3,4, and widespread chromosomal instability5. AT patients, on receiving conventional radiotherapy for tumour treatment, tend to develop unusually severe complications often culminating in premature death6–8. Pronounced radiosenitivity is also observed at the cellular level in laboratory studies; the number of radiation-induced chromosomal aberrations is enhanced in leukocytes obtained from AT donors9. Moreover, diploid fibroblasts cultured from affected individuals exhibit a reduced ability to form colonies following exposure to γ radiation10 and radiomimetic chemicals11. Since the principal damage induced by both types of agents occurs in the DNA and seems to be acted on by the same enzymatic repair mechanisms12,13, it would seem probable that the molecular basis for the clinical radiosensitivity of AT patients stems from a deficient DNA repair mechanism. We therefore measured the DNA repair properties of AT fibroblasts after exposure to γ radiation. Data presented below provide direct biochemical evidence that diploid strains from AT donors are indeed impaired in DNA repair; in particular, these cell lines possess an enzymatic defect in an excision-type repair process operating on γ-modified nitrogenous base residues.

Chemical Radioprotection and Radiosensitization of Mammalian Cells Growing in Vitro

Abstract: The radiosensitizing and radioprotective effects of various compounds have been characterized in Chinese hamster fibroblasts growing in vitro and in a model chemical system utilizing DNA as target. The contribution to the lethal action of ionizing radiation in mammalian cells from the indirect effect of OH has been measured. The data are consistent with the “oxygen fixation hypothesis,” whereby target free radicals react either with radical-reducing species, resulting in “chemical repair,” or with radical-oxidizing species, resulting in “fixation” of radical damage to a potentially lethal form. Radical repair–fixation competition has been demonstrated in the in vitro chemical system with a sensitizer other than O2. Dimethyl sulfoxide is shown to radioprotect in both the cellular and chemical systems by scavenging OH. Cysteamine, on the other hand, is shown to protect primarily by adding to the pool of radical-reducing species, resulting in enhanced repair of free-radical damage in the targets. Electron-af...