Chromosome and Genome Mutations

Non-mammalian test systems Mammalian assays Human cells Genome mutations  

In addition to the positive results collected in Table 9.3, experiments with a series of metals also yielded negative data which are not listed in the table. Li, K, Na, Ca, Al, Cu, Fe, Sb, and Zn were those found to be non-clastogenic in several (most) experimental assays. However, some of those metals presented in Table 9.3 also occasionally yielded negative results, this apparently being dependent upon the type of compound tested, as well as the experimental conditions. 

Combinations of certain test assays may provide a clearer view of the mutagenicity of metals if based on reliable comparative pilot studies. A comparison of the activity of metals in the micronudeus test and in 

Most of the data presented on chromosomal alterations or secondary aberrations induced by metals and their compounds have been obtained from short-term tests. However, Coen etal. (2001) showed that heavy metals of relevance to human health (e.g., Cd and Ni) may induce a long-term 

As many metal compounds exert a rather weak mutagenic effect, their carcinogenic action cannot be explained by this effect alone. However, in several cases, indirect genotoxic effects - namely synergism with known mutagens - may be one reason for their tumorigenicity. 

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Assays for Chromosomal and Genomic Mutations In vitro cytogenetic assay [OECD 473] / ... 

More than one-third of spontaneous abortions are caused by chromosomal and genomic mutations. Chromosomal mutations produce their effect mainly by predisposing the organism to transmit unbalanced combinations of chromosomes. 

Aside from conditions that are inherited as simple Hendelian dominants, the most completely understood class is that comprising chromosomal and genomic mutations. 

This usually means that the system should detect three major classes of mutation—genic, chromosomal, and genomic. Only with additional justification would other end points, such as chemical damage to DMA and mammalian cell transformation (neoplastic transformation), be recommended as part of a mutagenicity test battery. Such systems can be validated by demonstrating that they predict mutation. 

By far the most accurately determined incidences are those of gross chromosomal abnormalities—both chromosomal mutations (involving changes in chromosome structure) and genomic mutations (changes in chromosome number). A large fraction of the total impact of these is on the first two or three generations. The kinetics of expression of X-... 

CHROMOSOMAL MUTATION A mutational change that simultaneously affects many genes, in that it involves segments of chromosomes, rather than a single genetic locus. (See also GENE MUTATION, POINT MUTATION, and GENOMIC MUTATION)... 

The myopathic form of CPT deficiency is due to a defect of CPT II. The gene for CPT II has been localized to chromosome 1, and several mutations have been identified in patients [4]. As in the case of McArdle s disease (see above), one mutation, a serine-to-leucine substitution at codon 113, is far more common than the others in Caucasians and can be screened for in genomic DNA from blood cells, thus potentially avoiding muscle biopsy. 

GENOMIC MUTATION A change in the number of chromosomes in the genome that does not alter the structure or arrangement of genes in the chromosomes. (See also ANEUPLOIDY, POLYPLOIDY, CHROMOSOMAL MUTATION, GENE MUTATION, and POINT MUTATION)... 

Genome mutations. Genome mutations occur when the total number of chromosomes is altered (aneuploidy) (Russell, 1983). Polyploidy arises when an extra copy of every chromosome is made, and trisomy arises when only one extra copy of a single chromosome is present. If an entire chromosome is absent, the consequent disorder is called a monosomy. 

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