Sources, Effects and Risks of Ionizing Radiation

The development of the cytokinesis-block (CB) technique has transformed the human-lymphocyte micronucleus assay (MN) into a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in (a) patients undergoing fractionated partial-body radiotherapy and (b) rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring we performed extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various life-style factors. We have also developed a new variation to the CBMN assay that permits the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (UV, 254 nm) radiation and approximately 40-fold for methylnitrosourea. Consequently the CBMN assay can now be used to measure not only whole chromosome loss or chromosome breaks but also excision-repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should ensure its successful application in monitoring exposed populations as well as in identifying mutagen-sensitive individuals within a population.

The cytokinesis-block micronucleus technique: A detailed description of the method and its application to genotoxicity studies in human populations

(1983). Ionizing Radiation: Sources and Biological Effects. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 43, No. 5, pp. 585-586.

Ionizing Radiation: Sources and Biological Effects

This paper reviews the ability of a number of chemicals to induce sister-chromatid exchanges (SCEs). The SCE data for animal cells in vivo and in vitro, and human cells in vitro are presented in 6 tables according to their relative effectiveness. A seventh table summarizes what is known about the effects of specific chemicals on SCEs for humans exposed in vivo. The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.

Sister-chromatid exchanges: a report of the GENE-TOX program.

The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned from microbes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products.

http://s3.e-monsite.com/2011/03/02/83535046dna-damage-and-repair-in-plants-pdf.pdf

Dna damage and repair in plants

Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells.

The in vitro human lymphocyte assay for assessing the clastogenicity of chemical agents.

The yield of X-ray-induced chromosome aberrations in unstimulated human lymphocytes is greatly enhanced when the cells are incubated with cytosine arabinoside (ara-C) after irradiation. There is an increase in aberration yield with increasing time of incubation in ara-C (1, 2 or 3 h). When G 2 cells are X-irradiated and incubated with ara-C until fixation, the deletion yields are considerably increased, but no interchanges are observed. In the absence of ara-C, 0.29 interchanges per cell were observed. The G 2 results suggest that ara-C inhibits the repair of damage that leads to the formation of exchange aberations. The increase in yield in unstimulated lymphocytes is interpreted to be due to an accumulation of strand breaks caused by ara-C inhibition of repair; when the inhibition is reversed with deoxycytidine, these breaks can interact to form aberrations. A possible mechanism for the induction of chromosome aberrations by X-rays is offered on the basis of these results.

The effect of cytosine arabinoside on the frequency of X-ray-induced chromosome aberrations in normal human leukocytes.

Young adult male mice were injected intravenously with doses of methyl methanesulfonate(MMS) ranging from 25 to 100 mg/kg body weight. These males were serially mated to superovulated females from day 1 post injection to day 23 post injection. The morning after mating (about 4-6 h post-copulation) the females were sacrificed and ova flushed from the ampulla. The ova were cultured, in the presence of colchicine, for 26 h and metaphase preparations made of the first cleavage division. Chromosome analysis was done and the types, and extent, of chromosome aberrations correlated to previously published dominant lethal data at the same MMS doses and time intervals. The types of aberrations seen were predominantly double fragments (presumably isochromatid deletions), chromatid interchanges, and some chromatid deletions, as well as shattering effect on the male complement at the highest dose and the time of peak sensitivity to dominant lethal induction. When the frequency of cells containing a cytologically visible aberration is compared to the total dominant lethal data an excellent correlation is obtained. Furthermore, the frequency of highly damaged cells, agrees very well with estimated frequencies of preimplantation loss. These data strongly suggest that chromosome aberrations seen at the first cleavage stage are the basis of MMS-induced dominant lethality.

Studies on chemically induced dominant lethality. I. The cytogenetic basis of MMS-induced dominant lethality in post-meiotic male germ cells.

The frequencies of X-ray induced asymmetrical interchanges (dicentrics) and acentric fragments (deletions) at several doses were measured in the circullating leukocytes of six species. The leukocytes of the species used had similar DNA contents but different chromosome and chromosome arm numbers. The data for dicentrics were fitted separately for each species by regression analysis to the model Yj = bjD + cjD2. All species gave a good fit to this model. As expected, when the dicentric data for all species were pooled and fitted to this model a poor fit was obtained. However, if a term for arm number was included, so that the model Yj = (Nj−1) (bD+cD2) was fitted, a significant amount of the variation among species could be accounted for. At each dose there was an approximately linear relationship between the yield of dicentrics and the arm number. Man, with an effective arm number of 81, had twice as many dicentrics as the mouse, with an effective arm number of. These results strongly suggest that the chromosome arm number of a species influences the yield of asymmetrica interchanges. The chromosome arm number did not appear to influence the yield of deletions, and the yields induced in the mouse and man at easch dose were equal.

These results show that man is twice as sensitive as the mouse to the induction of translocations, whereas the two species are equally sensitive to the indcution of deletions and, in all probability, to the production of mutations.

R.J. Preston

Papers

Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells.

The in vitro human lymphocyte assay for assessing the clastogenicity of chemical agents.

The effect of cytosine arabinoside on the frequency of X-ray-induced chromosome aberrations in normal human leukocytes.

Studies on chemically induced dominant lethality. I. The cytogenetic basis of MMS-induced dominant lethality in post-meiotic male germ cells.

Genetic hazards of ionizing radiations: Cytogenetic extrapolations from mouse to man