NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells.

The method of alkaline elution provides a sensitive measure of DNA single-strand length distribution in mamalian cells and is applicable to a variety of problems concerning DNA damage, repair, and replication. The physical basis of the elution process was studied. The kinetics of elution above the alkaline transition pH were found to occur in two phases: an initial phase in which single-strand length is rate limiting, followed by a phase in which elution is accelerated due to the accumulation of alkali-induced strand breaks. The range of DNA single-strand lengths that can be discriminated by elution above the alkaline transition pH was estimated by calibration relative to the effects of x ray, and was found to be 5 X 10(8)-10(10) daltons. Shorter DNA strands elute within the pH transition zone, which extended from pH 11.3 to 11.7 when tetrapropylammonium hydroxide was used as base. This elution was relatively rapid, but was sharply limited by pH, according to the length of the strands: the length of the strands eluted increased with increasing pH. Alkaline elution was inhibited by treatment of cells with low concentrations of nitrogen mustard, a bifunctional alkylating known to cross-link DNA. On investigation of the possibility that DNA subclasses may differ in their elution behavior, satellite L strands were found to elute more slowly from cells exposed to a low dose of x ray than did the bulk DNA.

Fractionation of DNA from mammalian cells by alkaline elution

Improved microfluorometric DNA determination in biological material using 33258 Hoechst

Alkylating agents and compounds converted metabolically to alkylating agents form an important class of carcinogens and mutagens that includes a number of environmentally important /V-nitrosocompounds. A number of alkylating agents are also useful antitumor drugs. There are many factors determining the sensitivity to the toxic, mutagenic, and carcinogenic poten tial of these compounds (1-4).2 One of these is the capacity to

/pdf/mammalian-o6-alkylguanine-dna-alkyltransferase-regulation-58rg79j6q8.pdf

Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents.

Summary The technique of alkaline elution was applied to studies of DNA damage and repair in mouse leukemia L1210 cells treated with nitrogen mustard (HN2) and nitrosoureas. DNA cross-linking was measured in terms of the reduction in the effect of X-ray on the kinetics of DNA elution and was observed in cells treated with HN2 and three chloroethylnitrosoureas: 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and chlorozotocin. Evidence was obtained that cross-links are of two types, DNA interstrand cross-links and DNA-protein cross-links, distinguishable on the basis of sensitivity to proteinase-K. HN2 and 1,3-bis(2-chloroethyl)-1-nitrosourea each produced both types of cross-links. In most of the studies reported, the combined effect of the two types of cross-links was measured. With HN2, cross-linking was observed at subtoxic doses, and the cross-links were fully repaired by 24 hr. At higher HN2 doses, which reduced colony-forming ability, cross-links were not fully repaired by 24 hr. Cross-linking by chloroethylnitrosoureas differed from that by HN2 in that the effect increased for about 6 hr after removal of the drug (treatment times were 0.5 hr for HN2 and 1 hr for nitrosoureas). The chloroethylnitrosoureas, but not HN2, also produce DNA single-strand breaks or lesions, which were converted to single-strand breaks in alkali. Methylnitrosourea produced little or no cross-linking for at least 6 hr after treatment but did produce extensive DNA damage of the alkali-labile type; this damage was repairable and had little efect on colony-forming ability. Fluoroethylnitrosourea, the fluoro analog of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, was much less effective than 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in producing cross-links. The findings on the kinetics and structure dependence of cross-linking are similar to the previously reported findings on interstrand cross-linking of purified DNA and support a two-step reaction mechanism involving a chloroethylated intermediate.

https://cancerres.aacrjournals.org/content/canres/37/7_Part_1/2114.full.pdf

DNA Damage and Repair in Mouse Leukemia L1210 Cells Treated with Nitrogen Mustard, 1,3-Bis(2-chloroethyl)-1-nitrosourea, and Other Nitrosoureas

Bifunctional alkylating agents are known to produce cross-links between DNA and protein and between paired DNA strands. The possibility of discriminating these two classes of cross-links in L1210 cells treated with haloethylnitrosoureas or nitrogen mustard was explored with the alkaline elution technique. Two classes of cross-links were demonstrated, based on sensitivity to proteinase K; the proteinase-sensitive cross-links appear to be DNA-protein cross-links, and the proteinase-resistant class may include interstrand cross-links. Proteinase-sensitive cross-links form more rapidly than do proteinase-resistant cross-links in cells treated with chloroethylnitrosoureas, perhaps because these agents can chloroethylate protein sulfhydryl or amino groups followed by rapid reaction of these chloroethylated groups with DNA. Although both types of cross-links produced by nitrogen mustard disappeared or were repaired after 24 hr, the removal of cross-links produced by chloroethylnitrosoureas either did not occur or was incomplete in 24 hr. In addition to cross-links, cells treated with haloethylnitrosoureas exhibited DNA strand breaks; a method is suggested for estimating the apparent frequencies of strand breaks and cross-links in the DNA.

https://cancerres.aacrjournals.org/content/canres/38/10/3197.full.pdf

DNA-protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells.

The formation of DNA cross-links is thought to represent the lethal lesion following exposure of cells to blfunctional alkylating agents Since differences in rates of formation and repair of cross-links may explain differences in activity of these agents, we have studied these events following exposure of L1210 cells to nitrogen mustard (HN2) and melphalian With the technique of alkaline elution, it was possible to measure cross-linking at doses that result in relatively little cell kill Following a 30-min exposure to HN2, DNA cross-links increased for 1 to 2 hr and were then removed by a porcess that was virtually complete in 24 hr In contrast, following a 30-min exposure to melphalan, cross-link formation increased for 12 hr and removal was much slower than it was for HN2 Comparison of cell survival with cross-linking kinetics suggests that persistence of the cross-links with time is an important factor in determining lethality

Differences between Melphalan and Nitrogen Mustard in the Formation and Removal of DNA Cross-Links

Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was measured by alkaline elution in cells treated with four chloroethylnitrosoureas. Whereas VA-13 cells exhibited dose-dependent interstrand crosslinking, little or none was detected in IMR-90 cells. The IMR-90 cells, however, exhibited at least as much DNA-protein crosslinking as did VA-13 cells. The results can be interpreted in terms of a possible difference in DNA repair between the cell lines.

https://www.pnas.org/content/pnas/77/1/467.full.pdf

Regina A. G. Ewig

Papers

Fractionation of DNA from mammalian cells by alkaline elution

DNA Damage and Repair in Mouse Leukemia L1210 Cells Treated with Nitrogen Mustard, 1,3-Bis(2-chloroethyl)-1-nitrosourea, and Other Nitrosoureas

DNA-protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells.

Differences between Melphalan and Nitrogen Mustard in the Formation and Removal of DNA Cross-Links

DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.