Chromosome aberrations, breakage

Revell, S.H. (1974). The breakage-and-reunion theory and the exchange theory for chromosome aberrations induced by ionizing radiations A short history. In Advances in Radiation Biology (Lett, J.T. and Zelle, M., Eds.). Vol. 4, Academic Press, New York, pp. 367-415. 

Stmctural chromosome aberrations may be of two types, chromosome or chromatid. A chromo-some-type aberration is a stmctural chromosome damage expressed as breakage, or breakage and... 

In vivo, neither covalent binding to DNA nor DNA strand breakage was induced in several studies on rat liver, and unscheduled DNA s mthesis was not induced in the liver of either rats or mice. Gene mutations were not induced in the liver of dosed mice in a single study and there was no evidence for induction of chromosomal aberrations in mice or rats. Aberrations were induced, however, in the embryos of dosed pregnant Syrian hamsters. Dominant lethal effects were reported to be induced in male mice, but re-evaluation of these data did not confirm this conclusion. 

Induction of DNA single-strand breakage in rat liver after in-vivo exposure to N-nitrosodiethanolamine was demonstrated in three studies and dose-dependent effects were shown. In one of these studies, the DNA strand-breaking potential of 7V-nitroso-diethanolamine was found to be abolished by inhibition of sulfotransferase by 2,6-dichloro-4-nitrophenol. Unscheduled DNA synthesis was not detected in rats or mice in an in-vivo/in-vitro hepatocyte DNA repair assay after treatment with 7V-nitrosodi-ethanolamine. A single study in mice exposed in vivo to 7V-nitrosodiethanolamine did not find any significant induction of structural or numerical chromosomal aberrations or micronuclei in bone-marrow cells. 

In cultured mammalian cells, acrylonitrile induced DNA strand breakage, gene mutation, sister chromatid exchanges and chromosomal aberrations, but not aneuploidy or unscheduled DNA synthesis in rat hepatocytes, at least if the silver grain counting method was used. [Studies using the less reliable scintillation counting method have not been summarized.] Cell transformation was induced in several test systems and gap-junctional intercellular communication was inhibited in one study with Chinese hamster V79 cells. 

In studies with human cells in vitro, acrylonitrile induced DNA strand breakage in a single study, gene mutations in two studies and sister chromatid exchanges in two of three studies, but not unscheduled DNA synthesis or chromosomal aberrations in single studies. 

Ethylene dibromide is mutagenic in bacteria and Drosophila, and in rodent and human cells in vitro. It induced DNA breakage but not chromosomal aberrations or micronuclei in vivo in rodents. It gave negative results in dominant lethal tests in mice and rats. It did not induce either chromosomal aberrations or sister chromatid exchange in humans in vivo. 

We can measure three different types of mutations in animals (a) chromosome aberrations in germ cells and in mitotic cells, (b) dominant-lethal mutations, and (c) specific-locus mutations. In the first two systems, we measure the induction of chromosome breakage and in the latter system we measure point mutations and chromosome deletions. 

Chromosome aberrations. Ionizing radiations break chromosomes presumably through DNA double-strand breakage (2, 3) and are capable of inducing aberrations in all phases of the cell cycle. 3AB potentiates the induction of chromosome aberrations by sparsely ionizing radiations, such as X- and y-rays (4-7), but does not affect the yields induced by densely ionizing fast neutrons (4). This indicates that poly(ADP-ribose) plays a different role in response to these types of radiation. 

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