Abschlussarbeit PGS Toxikologie Dr. Martin Willi Herbert Krug
Novel methods for the assessment of genotoxic risks - Summary
Cancer is one of the leading causes of death in Western countries. Since the therapeutic options for the treatment of this disease are still limited, establishing efficient strategies for cancer prevention is essential. The most important issue in cancer prevention is the identification of factors that initiate and promote the development of a neoplastic disease.
To minimize the exposure of the public to genotoxic chemicals, it is essential to determine the genotoxic risk that is associated with new chemical entities - e.g., industrial chemicals, cosmetic and pharmaceutical ingredients, and pesticides - before placing them on the market. For this reason, various batteries of in vitro and in vivo genotoxicity tests have been established. However, the tests that are currently used in these test batteries suffer from several weaknesses: Especially the assays in mammalian cells have a tendency to produce falsely positive results and allow for an only rather low throughput. Accordingly, new in vitro genotoxicity tests that are reliable, easy to perform, and achieve a high sample throughput are urgently needed.
The purpose of the present study was to identify scientific literature on important novel in vitro assays for the assessment of genotoxicity. To identify the scientific literature on novel test systems, a series of database searches was conducted using the search engine PubMed that covers the databases MEDLINE, OLDMEDLINE, and PubMed Central. Additional internet searches were performed using the search engine Scirus.
Eight emerging, non-standard assay systems were identified by these database searches: Three bacterial assays that use the prokaryotic SOS response (the Vitotox® test, the umu test, and the Mutatox® test), two yeast cell-based test systems [the yeast deletion (DEL) and recombination as- say and the GreenScreen GC assay], one test in human cells (the GreenScreen HC assay), one assay for induction of micronuclei (MN) in hen's eggs, named the hen's egg test for micronuclei (HET-MN test), and finally the Syrian hamster embryo (SHE) cell transformation assay, an assay that measures the conversion of normal mammalian cells to the preneoplastic phenotype. Addition- ally, various toxicogenomic methods were identified in the current database search and information on these methods was compiled in a respective chapter of this work.
On the basis of the identified data, the properties and the current state of each assay were de- scribed in the present work, and an estimation of the further perspectives of each assay was given.
This analysis revealed that the eight assay systems examined differ widely from one another with respect to their mode of operation, performance, and the degree up to which they have been de- veloped until now.
In summary, it was found that some of the identified in vitro methods represent valuable tools that can detect a broad range of genotoxic compounds, are relatively inexpensive and fast, and can be performed in high throughput. Accordingly, these novel methods can complement the established in vitro assays and may therefore help to facilitate and accelerate testing for genotoxicity, although they may not replace the current test batteries in the foreseeable future.
