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Induction of sister-chromatid exchanges in vivo
162 combined with poor differential staining, or to another effect (BUdR incorporation).
20 Bayer, U., CNRS, F-94800 Villejuif (France)
Induction of sister-chromatid exchanges in vivo Dividing cells and the incorporation of BUdR in DNA are the prerequisites for the SCE test. Therefore, every tissue which fulfils these 2 conditions can be used. A comparison of results of 24 substances obtained by the SCE test in vivo with 6 other most c o m m o n l y used tests presents the SCE test in vivo as being sensitive, reliable and economic to examine the effects of chemicals on DNA. Negative results with mutagens in the SCE test in vivo may be due to (1) mitotic inhibition, (2) direct influence of the test substance on the BUdR/ thymidine incorporation, (3) extremely short-lived active forms, and (4) organ o t r o p y of the test compound. Provided that the lowest and highest effective doses were determined, dose curves of the SCE test in vivo show the sigmoid shape. Site, steepness and saturation value of the curve are determined by the quotient of DNA damage visible by SCE induction and the cytotoxic effects of the active form of the test substance. Dose--response curves of several substances are discussed under the aspect of possible conclusions on pharmacological properties of substances being tested.
21 Graf, U., T. Skripsky and F.E. Wiirgler, Institute of Toxicology, Swiss Federal Institute of Technology and University of ZiJrich, CH-8603 Schwerzenbach (Switzerland)
Sister-chromatid exchanges and ring chromosome losses in Drosophila melano-
gaster Sister-chromatid exchanges (SCE) can be demonstrated cytologically in neural ganglia of third instar larvae of Drosophila melanogaster. Cytological studies with a ring-X chromosome showed that SCEs are the basis of dicentric rings which can lead to the loss of the ring chromosome (Gatti et al., Genetics, 91 (1979) 255--274). The registration of ring-X chromosome losses in crosses with suitably marked strains is therefore a simple test system for mutageninduced SCEs. Males carrying a ring-X chromosome are treated with the mutagen and crossed to females with normal free X-chromosomes. Ring-X losses are then scored in the progeny as phenotypically recognizable XO-males. A first series of experiments with X-rays showed that maternal effects -- which are the expression of the polygenic control of m u t a t i o n fixation -- influence the rates of ring-X losses. It was tried to induce ring-X losses with the alkylating agents MMS, EMS, HN2, MNNG and MMC. Of these agents, MMC was the most efficient, EMS the weakest agent in inducing ring-X losses. An analysis of the
20 Bayer, U., CNRS, F-94800 Villejuif (France)
Induction of sister-chromatid exchanges in vivo Dividing cells and the incorporation of BUdR in DNA are the prerequisites for the SCE test. Therefore, every tissue which fulfils these 2 conditions can be used. A comparison of results of 24 substances obtained by the SCE test in vivo with 6 other most c o m m o n l y used tests presents the SCE test in vivo as being sensitive, reliable and economic to examine the effects of chemicals on DNA. Negative results with mutagens in the SCE test in vivo may be due to (1) mitotic inhibition, (2) direct influence of the test substance on the BUdR/ thymidine incorporation, (3) extremely short-lived active forms, and (4) organ o t r o p y of the test compound. Provided that the lowest and highest effective doses were determined, dose curves of the SCE test in vivo show the sigmoid shape. Site, steepness and saturation value of the curve are determined by the quotient of DNA damage visible by SCE induction and the cytotoxic effects of the active form of the test substance. Dose--response curves of several substances are discussed under the aspect of possible conclusions on pharmacological properties of substances being tested.
21 Graf, U., T. Skripsky and F.E. Wiirgler, Institute of Toxicology, Swiss Federal Institute of Technology and University of ZiJrich, CH-8603 Schwerzenbach (Switzerland)
Sister-chromatid exchanges and ring chromosome losses in Drosophila melano-
gaster Sister-chromatid exchanges (SCE) can be demonstrated cytologically in neural ganglia of third instar larvae of Drosophila melanogaster. Cytological studies with a ring-X chromosome showed that SCEs are the basis of dicentric rings which can lead to the loss of the ring chromosome (Gatti et al., Genetics, 91 (1979) 255--274). The registration of ring-X chromosome losses in crosses with suitably marked strains is therefore a simple test system for mutageninduced SCEs. Males carrying a ring-X chromosome are treated with the mutagen and crossed to females with normal free X-chromosomes. Ring-X losses are then scored in the progeny as phenotypically recognizable XO-males. A first series of experiments with X-rays showed that maternal effects -- which are the expression of the polygenic control of m u t a t i o n fixation -- influence the rates of ring-X losses. It was tried to induce ring-X losses with the alkylating agents MMS, EMS, HN2, MNNG and MMC. Of these agents, MMC was the most efficient, EMS the weakest agent in inducing ring-X losses. An analysis of the