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First EEMS training course on somatic genotoxicity assays with Drosophila
Mutation Research, 216 (1989) 89-90 Elsevier
89
MTR 08720
Meeting Report
First EEMS training course on somatic genotoxicity assays with Drosophila Under the auspices of the European Environmental Mutagen Society (EEMS) a first training course on the Somatic Mutation And Recombination Tests (SMART) with Drosophila was held at the Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, in CH-8603 Schwerzenbach near Zurich (Switzerland), from September 12 to 23, 1988. The 15 participants came from 10 different countries: Brazil (1), Federal Republic of Germany (2), India (2), Italy (1), Mexico (2), Poland (1), South Korea (1), Switzerland (1), Turkey (1) and The United States (3). The faculty consisted of F.E. Wiirgler, E.W. Vogel, U. Graf, H. Frei, A. FriSlich and A. Surjan. In recent years, new developments in the field of genetic toxicology testing, in particular the evaluations of several international collaborative studies, led to a reappraisal of the potential use of Drosophila assays for genotoxicity testing. In Drosophila, the assay validated with the largest number of chemicals is the sex-linked recessive lethal test. Although for genotoxins other than directly-acting agents and promutagens with single-step activation the sensitivity of the test is relatively low (0.33-0.79), the specificity is especially high (0.86-1.0). From this it was concluded that, in general, positive results in Drosophila are valid predictors of potential genotoxicity in mammals. On the other hand, the use of Drosophila germ cell assays as specific predictors of a genotoxic potential in particular germ cell stages of mammals, has failed to a certain extent. The possibility of such a specific organ to organ extrapolation is not substantiated by toxicological experience. Thus, the value of Drosophila has to be seen as a predictor of mammalian genotoxicity in a broad sense, but certainly not for specific organs. If this concept is accepted, one will argue that for the detection and quantification of the genotoxic potential of a chemical, germ cells as well as
somatic cells of Drosophila may be suited. It was against this background that a number of assays based on the detection of somatic mutation and mitotic recombination were developed, which are presently validated in different laboratories. These comparatively fast and inexpensive tests are rather sensitive. They detect genotoxins inducing genetic changes in mitotically dividing blastemas of Drosophila larvae. The effects are scored later as mosaic spots on adult structures of the flies, such as the wing (multiple wing hairs/flare test) or the eye (white/white + test, white/white-coral test, unstable-zeste test and white-ivory test). Calibration studies, soon to be completed for the eye and for the wing systems, indicate that the multiple wing hairs/flare test and the white/white + test are best suited for screening purposes. Therefore the practical work, which comprised about 70% of the time in the training course, concentrated on these two assays. The participants had the opportunity to learn and practise all the steps involved in these two tests. The other assays were presented in demonstrations, and their specific potentials and limitations were discussed. Participants not yet familiar with Drosophila were introduced to the biology of Drosophila (eggs, larvae, pupae, adults, genetic traits). They were shown the handling and rearing of flies in practice and could gain an insight into the organization of a Drosophila laboratory. Practical work with the two screening assays included handling of adults and larvae, exposure of larvae to chemicals (including laboratory safety measures, decontamination and mutagenie waste management), collection and storage of flies from controls and exposed groups, preparation of flies, mounting of wings, scoring of mosaic spots in eyes and wings, computer analysis of the data, statistical evaluation of spot frequencies as well as data interpretation. Lectures and seminars held daily in the morning and the late afternoon made the participants
0165-1161/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
90
familiar with the theoretical aspects of the somatic assays (genetic basis, developmental aspects, metabolism of xenobiotics in Drosophila, D N A repair, theoretical basis of the statistics used to define positive, negative and inconclusive results, data reporting) as well as with the conceptional and practical implications of the testing strategies. During the practical working sessions and during the afternoon seminars, many occasions were found for animated discussions among participants and staff. We are confident that the 15 participants have gathered sufficient knowledge and information during the course to carry out the tests and have practised to an extent enabling them to establish the Drosophila somatic assays in their own institutions. The two laboratories (Schwerzenbach and Leiden) engaged in the course agreed to provide, to the best of their possibilities, advice and help also in the future to the participants and their respective laboratories. We are grateful to all collaborators at the laboratory in Schwerzenbach who helped us in a
friendly mood to achieve the goals set out for the course. We would also like to thank especially all institutions and companies who sponsored the course. In particular the Directorate for Development Cooperation and Humanitarian Aid of the Swiss Federal Department of Foreign Affairs, Berne, and the Stanley Thomas Johnson Foundation, Berne, by their most generous support, made it possible that several trainees from developing countries could participate in the training course. We are especially grateful for this support because the techniques for genotoxicity testing presented in the course seem particularly useful in laboratories of third world countries. F.E. WSrgler a E.W. Vogel b a Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, Schwerzenbach (Switzerland) b Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Leiden (The Netherlands)
89
MTR 08720
Meeting Report
First EEMS training course on somatic genotoxicity assays with Drosophila Under the auspices of the European Environmental Mutagen Society (EEMS) a first training course on the Somatic Mutation And Recombination Tests (SMART) with Drosophila was held at the Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, in CH-8603 Schwerzenbach near Zurich (Switzerland), from September 12 to 23, 1988. The 15 participants came from 10 different countries: Brazil (1), Federal Republic of Germany (2), India (2), Italy (1), Mexico (2), Poland (1), South Korea (1), Switzerland (1), Turkey (1) and The United States (3). The faculty consisted of F.E. Wiirgler, E.W. Vogel, U. Graf, H. Frei, A. FriSlich and A. Surjan. In recent years, new developments in the field of genetic toxicology testing, in particular the evaluations of several international collaborative studies, led to a reappraisal of the potential use of Drosophila assays for genotoxicity testing. In Drosophila, the assay validated with the largest number of chemicals is the sex-linked recessive lethal test. Although for genotoxins other than directly-acting agents and promutagens with single-step activation the sensitivity of the test is relatively low (0.33-0.79), the specificity is especially high (0.86-1.0). From this it was concluded that, in general, positive results in Drosophila are valid predictors of potential genotoxicity in mammals. On the other hand, the use of Drosophila germ cell assays as specific predictors of a genotoxic potential in particular germ cell stages of mammals, has failed to a certain extent. The possibility of such a specific organ to organ extrapolation is not substantiated by toxicological experience. Thus, the value of Drosophila has to be seen as a predictor of mammalian genotoxicity in a broad sense, but certainly not for specific organs. If this concept is accepted, one will argue that for the detection and quantification of the genotoxic potential of a chemical, germ cells as well as
somatic cells of Drosophila may be suited. It was against this background that a number of assays based on the detection of somatic mutation and mitotic recombination were developed, which are presently validated in different laboratories. These comparatively fast and inexpensive tests are rather sensitive. They detect genotoxins inducing genetic changes in mitotically dividing blastemas of Drosophila larvae. The effects are scored later as mosaic spots on adult structures of the flies, such as the wing (multiple wing hairs/flare test) or the eye (white/white + test, white/white-coral test, unstable-zeste test and white-ivory test). Calibration studies, soon to be completed for the eye and for the wing systems, indicate that the multiple wing hairs/flare test and the white/white + test are best suited for screening purposes. Therefore the practical work, which comprised about 70% of the time in the training course, concentrated on these two assays. The participants had the opportunity to learn and practise all the steps involved in these two tests. The other assays were presented in demonstrations, and their specific potentials and limitations were discussed. Participants not yet familiar with Drosophila were introduced to the biology of Drosophila (eggs, larvae, pupae, adults, genetic traits). They were shown the handling and rearing of flies in practice and could gain an insight into the organization of a Drosophila laboratory. Practical work with the two screening assays included handling of adults and larvae, exposure of larvae to chemicals (including laboratory safety measures, decontamination and mutagenie waste management), collection and storage of flies from controls and exposed groups, preparation of flies, mounting of wings, scoring of mosaic spots in eyes and wings, computer analysis of the data, statistical evaluation of spot frequencies as well as data interpretation. Lectures and seminars held daily in the morning and the late afternoon made the participants
0165-1161/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)
90
familiar with the theoretical aspects of the somatic assays (genetic basis, developmental aspects, metabolism of xenobiotics in Drosophila, D N A repair, theoretical basis of the statistics used to define positive, negative and inconclusive results, data reporting) as well as with the conceptional and practical implications of the testing strategies. During the practical working sessions and during the afternoon seminars, many occasions were found for animated discussions among participants and staff. We are confident that the 15 participants have gathered sufficient knowledge and information during the course to carry out the tests and have practised to an extent enabling them to establish the Drosophila somatic assays in their own institutions. The two laboratories (Schwerzenbach and Leiden) engaged in the course agreed to provide, to the best of their possibilities, advice and help also in the future to the participants and their respective laboratories. We are grateful to all collaborators at the laboratory in Schwerzenbach who helped us in a
friendly mood to achieve the goals set out for the course. We would also like to thank especially all institutions and companies who sponsored the course. In particular the Directorate for Development Cooperation and Humanitarian Aid of the Swiss Federal Department of Foreign Affairs, Berne, and the Stanley Thomas Johnson Foundation, Berne, by their most generous support, made it possible that several trainees from developing countries could participate in the training course. We are especially grateful for this support because the techniques for genotoxicity testing presented in the course seem particularly useful in laboratories of third world countries. F.E. WSrgler a E.W. Vogel b a Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, Schwerzenbach (Switzerland) b Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Leiden (The Netherlands)