Numerical aberrations

The spermatogonial test is used to identify substances that cause structural chromosome aberrations in mammalian spermatogonial cells, and is designed to investigate whether somatic cell mutagens are also active in germ cells. This test is not designed to measure numerical aberrations and is not routinely used for this purpose. 

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). 

Standard forms are used to score 100 to 200 cells for gaps, breaks, fragments, reunion figures, and numerical aberrations such as polyploidy cells... 

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. 

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. 

In addition, the assay can be used for the detection of compounds that induce polyploidies. An increase in the number of polyploidy cells may indicate that a compound has the potential to induce numerical aberrations. 

Nonrandom patterns of numerical aberrations are frequently observed in cancer cells, implicating aneuploidy in carcinogenesis. Associations between... 

Different types of analyses for the detection of micronuclei originating from structural or numerical aberrations are used light microscopy, semiautomated imaging systems, and flow cytometry (FACS analysis) [66, 67], Fluorescent in situ hybridization (FISH) with specific probes (e.g., centromeric probes) can also be used to examine nondisjunctions. Depending on the methodology, specific features of the damage can be characterized and mechanisms of action addressed. 

Numerical aberrations of chromosomes or chromosomal segments Numerical chromosomal aberrations, complete or segmental, are found in many malignant tumors, mainly in late, undifferentiated and anaplastic stages (G3-G4). 

CldUrd does not induce chromosomal aberrations when cells are grown for only 12 h in the analogue [9]. However, incubation for 24 h in medium containing 100% CldUrd results in numerous aberrations, which are all of the chromatid type (Table 2). Treatment with a low dose of 3AB (1 xaM) increases this frequency. At 10 mAf the mitotic index is drastically decreased and less aberrations are observed. 

In contrast to the finding that SAB does not induce chromosomal aberrations in CHO cells when BrdUrd is incorporated (to moderate levels) [10) treatment of cells with SAB simultaneously with the incorporation of QdUrd results in an increased frequency of aberrations. When high doses of SAB are used this increase is levelled down most probably it reflects the selection of less damaged cells due to the immense delay during S-phase of the damaged cells. Numerous aberrations are present in G2... 

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