ISSN:
1432-0738
Keywords:
Mutation
;
Chromosome aberration
;
Mutation test protocol
;
Mammalian risk evaluation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract During the past ten years growing concern about damage to DNA as an important cause of human ill-health has resulted in an explosive development of the field of genetic toxicology. Adequate regulations to restrict exposure to chemical mutagens require recognition and evaluation of mutagenic activity. For this purpose a qualitative and an extrapolation phase can be distinguished. For the qualitative phase, the minimal battery should consist of at least three tests, that is: (1) tests for gene- or point mutations in bacteria (Salmonella or E. coli) with and without metabolic activation; (2) two tests for point mutations in eukaryotes, or (3) one such test and a test for the detection of chromosome aberrations in mammalian cells in vitro. Depending on experience and facilities, a choice of two can be made out of the following four test systems: (1) Tests for point mutations in mammalian cells in vitro, with and without metabolic activation (deficiency for HGPRT, or TK); (2) the sex-linked recessive lethal test with Drosophila melanogaster; (3) tests with yeast, Saccharomyces cerevisiae, for point mutations, with and without metabolic activation; (4) tests for chromosome aberrations in mammalian cells in vitro, with and without metabolic activation. Two different metabolic activation systems should be employed. For further selection of more sensitive test systems, studies on comparative mutagenesis are considered important. A mammalian test for chromosome aberrations in vivo is not included in this minimal battery. Since under in vivo conditions considerably lower concentrations have to be employed than in vitro, it seems unlikely that positive results will be obtained with an in vivo mammalian cytogenetic assay, following negative results in an in vitro cytogenetic assay or in two different tests for point mutations. The finding that the effective concentration for the production of chromosome breakage events differs from that required to induce point mutations (the two-level effect) will be briefly discussed. When mutagenic compounds are indispensible or, in the case of ubiquitous exposure, a quantification of risks becomes necessary and here one is confronted with many difficulties. Information on damage that is hard to measure directly can be obtained in an indirect way by comparison with end-points that can be determined experimentally, such as alkylation per nucleotide.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00361242
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