Structural aberrations

In nickel refinery workers exposed to nickel chloride and nickel sulphate, only an increase in chromatide gaps (a doubtful type of structural aberrations) was observed [449]. By contrast, there was no increase of the mean sister chromatide exchange value in the group of nickel workers, as compared with the control group. 

The ability of the interphase cytogenetics technique to detect both numerical and structural aberrations in interphase nuclei of leukemia was referred to earlier in this paper. 

Gene mapping detection of heteromorphisms and determination of parental origin of heteromorphisms Detection of gene mutations Characterization of structural aberrations Identification of marker chromosomes Characterization of tumor cells Chromosome and karyotype evolution Spatial topography of chromosomes... 

Chromosomal mutations are recognised as morphological alterations in the gross structure of chromosomes, that is, they are structural aberrations which can be detected microscopically. Compounds which cause chromosome damage are called clastogens. 

Brown WM, Buckton KE, Langlands AO, et al. 1967. The identification of lymphocyte clones with chromosome structural aberrations in irradiated men and women. Int J Radiat Biol 13 155-169. 

The appearance of structural aberrations in chromosomes of peripheral lymphocytes is a sensitive indicator of exposure to agents that break chromosomes directly.115 117 This technique has been especially useful in studies of populations exposed to ionizing radiation.21 38 1+6 116 254 1+26 Some chemicals are known to cause similar effects in experimental organisms. Relatively small numbers of persons are required to show a moderate effect, and many of the aberrations are detectable long after the exposure.21 1+8 426... 

Chromosomal aberrations include both numerical and structural aberrations. Numerical aberrations are changes in the number of chromosomes of the normal number characteristic of the animals utilized (aneugenicity). Structural aberrations are classified into two types, chromosome or chromatid aberrations (clastogenicity). Chromosomal mutations and related events are the cause of many human genetic diseases and there is evidence that chromosomal mutations and related events are involved in cancer development. 

The MLA is used for the detection of point mutations, structural aberrations and aneugenicity. The principle of the assay is that cells deficient in thymidine kinase (TK) due to the tk+/" or tk/ mutation are resistant to the cytotoxic effects of the pyrimidine analogue trifluoro-thymidine (TFT). TK proficient cells are sensitive to TFT. This influences the cellular metabolism and leads finally to an inhibition of further cell division. Thus mutant cells are able to proliferate in the presence of TFT, whereas normal cells, which contain TK, are not. The major advantage of the assay is its ability to detect a broad range of mutagenic events represented by optimal detection of both large and small colonies. 

In addition, while the spectrum of mutations detected by the assay is very broad, it should be noted that not all such events are always detected with equal efficiency following treatment with particular test substances. Especially for the detection of structural aberrations and aneugenicity the recommended conditions of the protocol should be kept in detail. 

This in vitro cytogenetic test is a clastogenicity test system for the detection of chromosomal aberrations in cultured mammalian cells or primary cultures. Chromosomal aberrations may be either structural or numerical. However, because cytogenetic assays are usually designed to analyze cells at their first posttreatment mitosis and numerical aberrations require at least one cell division to be visualized, this type of aberration is generally not observed in a routine cytogenetic assay. The best estimate of aberration frequency is the first cell division after the start of treatment. Structural aberrations are of two types chromosome or chromatid aberrations. 

We can not absolutely discount the possibility that the observed loss in transition state binding is indirectly due to minor structural aberrations in the enzyme as a result of the substitutions. However, the crystal structure of 6-galactosidase, which became available near the completion of this study, shows that His-357 and His-391 are near the known active site residues and probably line the active site cavity (24). Therefore, they have the potential to form direct interactions with the substrate in the transition state form. 

Similarly, there was no correlation between urinary mercury levels (60-245 g/L) or the duration of exposure (11-34 years) and increased frequency of structural aberrations and micronuclei in the lymphocytes of 29 male workers exposed to mercury fulminate (Anwar and Gabal 1991). From the overall results, the authors concluded that mercury in the manufacturing process may not have been the clastogen. Other genotoxicity studies are discussed in Section 2.5. 

Several studies were located regarding genotoxic effects in humans after oral exposure to organic mercury. A positive correlation between blood mercury levels and structural and numerical chromosome aberrations was found in the lymphocytes of 23 people who consumed mercury-contaminated fish (SkerfVing et al. 1974). However, several factors preclude acceptance of these findings as valid. With respect to the increased incidence of structural aberrations, smokers were not identified, it was unclear whether chromatid and chromosome gaps were excluded from the evaluation, and significant effects... 

Syrian hamsters (oocytes) Structural aberrations - Mailhes 1983... 

In chronic myeloid leukemia, a translocation involving chromosomes 9 and 22 [t(9 22)] is seen in over 90% of the patients who have Philadelphia chromosome. In acute myeloid leukemia, certain structural aberrations are specifically associated with particular morphologic subtypes. Thus in the differentiation of the granulocytic lineage, a t(8 22) is associated, whereas a t(15 17) is seen only in promyelocytic leukemia. Monoblastic leukemia is associated with a translocation or deletion of the long arm of chromosome 12. 

Wistar male rats, 30 days old CAs Pb (acetate), 10 mg/kg, 5 X / week, 4 weeks, co-administered cypermethrin Pb acetate induced increase in aneuploidy and % damaged cells both agents together increased structural aberrations Nehez et al. (2000)... 

First cytologic alterations of colon adenocarcinoma cells (Fig. 43) manifested 12 h after administration of I and consisted of nuclear changes (Fig. 44) such as chromatin condensation, enlargement of the nuclear envelope, structural aberrations of the nucleoli and formation of segmented nuclei. Cytoplasmic phenomena occurred 12 h later and manifested by the appearance of lipid droplets and inclusion bodies which often contained cellular debris (Figs. 45, 46). These phenomena indicated cytoplasmic degeneration as well as phagocytotic activity of tumor cells. 

Advances in both liquid and solid NMR techniques have so changed the picture that it is now possible to obtain detailed information about the mobilities of specific chain units, domain structures, end groups, branches, run numbers, number-average molecular weights, and minor structural aberrations in many synthetic and natural products at a level ofl unit per 10,000 carbon atoms and below. — J. C. Randall [20]... 

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