Numerical chromosome change

The same chromosome aberration assay described above can be used to detect numerical chromosome changes (i.e., aneuploidy) in bone marrow cells. Chemicals that cause chromosome damage in germ cells can be detected using in vivo assays, either the dominant lethal assay, a test for structural chromosome aberrations in spermatogonia, or a more preferred test, the mouse heritable translocation assay. 

Numerical chromosomal change, which is the loss or duplication of the entire chromosome... 

Other cytogenetic abnormalities were also described in association with synovial sarcoma. These abnormalities are non-specific for this tumor and mainly numerical chromosomal changes such as +2, +4, +7, +8, +9, +12, +15, —3, —11, —14, —17 and —22. 

To determine the presence of aneugenes and clastogenes by means of in vivo method (B12-TG 474, OECD, 1997c), the micronuclens in cell lines is a method to partially replace laboratory animals. The purpose of the in vitro micronuclens assay is to identily agents that cause structural and numerical chromosome changes. The in vitro micronucleus test may employ cultures of established cell lines or primary cell cnltnres (Evans, 1976). However, until now OECD test guidelines for this method have not been snbmit-ted, nor has any formal valid method been found yet. 

Positive results in the mammalian in vivo bone marrow chromosome aberration test indicate that a substance induces stmctural chromosome aberrations in the bone marrow of the species tested. An increase in polyploidy (a multiple of the haploid chromosome number (n) other than the diploid number, i.e., 3n, 4n and so on) may indicate that a substance has the potential to induce numerical aberrations (change in the number of chromosomes from the normal number characteristic of the animals utilized). 

The test is used to identify subsfances that cause stmctural chromosome aberrations in cultured mammalian cells. A structural chromosome aberration is a change in chromosome structure detectable by microscopic examination of the metaphase stage of cell division, observed as deletions and fragments, intrachanges or interchanges. This test is not designed to measure numerical aberrations and is not routinely used for that purpose. 

All eucaryotic cells contain various proteins in their cytoplasm that interact to form mechanically stabilizing structures. The amounts of these proteins differ with cell type, and the structural elements - collectively referred to as the cytoskeleton -can be very labile. Labile transformations of cytoskeletal networks are involved in such essential biological phenomena as chromosome movement and cell division, intracellular material transport, shape changes relating to tissue development, and amoeboid-like locomotion (1-3). A great deal of work in recent years has led to the biochemical characterization of numerous cytoskeletal proteins(A) and the elucidation of their spatial localization within a cell(2). However, few quantifiable models yet exist that are appropriate for incorporating that information into notions of shape transformation and cell movement(5-8). 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

Induction of morphological transformation of SHE cells can occur in the absence of detectable induction of gene mutations measured concomitantly in the same cells (Barrett et al, 1983). Diethylstilbestrol and asbestos are two examples of chemicals that incluce cell transformation but not gene mutations (Barrett et al, 1981, 1983). However, a gcxxl correlation is observed between induction of chromosomal mutations (numerical and structural changes) and induction of cell transformation (Barrett etol, 1983 Oshimiueerol, 1984). 

Aberrations in newborn persons consist of both numerical changes (due primarily to nondisjunction) and structural deletions and rearrangements (due to chromosomal breakage). There has been no unambiguous demonstration in human beings that mutagens can cause nondisjunction. An additional problem, insofar as monitoring is concerned, is that the trisomies and monosomies seen in newborn persons also cause increased risk of abortion, Therefore, only an unknown fraction survive to birth. 

Numerical changes Structural changes in chromosomes in chromosomes... 

The same problems occur for theories about chromosome damage, reduction in testosterone production and so on. These areas have been studied thoroughly. It has been found that numerous substances affect testosterone production, but as changes are within a reasonable range it is a matter of no concern. In fact, we don t even know what it means that testosterone levels go up and go down day by day or hour by hour. 

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. 

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