The development and checking of a quick-test to determine the mutagenic and carcinogenic effects of chemicals in the same cell system in order to avoid animal testing

Status:

completed 07/1995

Aims:

The evaluation of dangerous substances is more complex when mutagenic/carcinogenic potential exists. A reliable in- vitro-examination must include all three biological terminal points (the mutation of genes, chromosomes, genomes). The analytic options require improvement with regard to practicability and sensitivity and the genotoxicity tests which were introduced do not, to date, include aneuploide-induction. Goal: improving the testing and evaluation of dangerous substances; reducing/avoiding necessary test on animals for this purpose.

Activities/Methods:

Micro-nuclear tests with fibroblasts from Syrian hamsters (SHE); (further) development of cytofluorometric methods to determine micro-nuclear induction, unscheduled DNA-synthesis, cell transformation to a microscopic overall analysis of micro-nuclear development in living cells which can differentiate between mitosis disorders and clastogenic effects.

Results:

The SHE micro-nuclear test validated with the investigation of approx. 90 substances (of which 65 are known to be carcinogenic/non-carcinogenic) can replace the in-vivo micro- nuclear test (mouse bone marrow) and additionally offers decisive advantages: no exogenous metabolisation necessary, high predicative value, relatively low cost, can be made automatic, sufficiently precise to establish dosage-effect relationships. The DNA fluorescence process on the mounting preparation is more suitable for quantitative evaluation than the cytofluorometric process. In tests with asbestos fibres a dependence between type of asbestos and dosage was demonstrable.

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