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Mutagenicity of Mysoline in spermatogenesis of mice
204
4TH ANNUAI.MEETING. HEIDELBERG
15 ADLER, I.-D., Abteilung ftir Genetik, Gesellschaft ffir Strahlen- und Umweltforschung, D-8o42 Neuherberg (W. Germany)
Primordial germ cell sensitivity to mutagenic effects of T E M Trietllylenemelainine (TEM) is known t o induce specific locus nmtations and translocations in mouse spermatogonia (CATTANACH, Mutation Res., 3 (r066) 346; CATTANACHAND WILLIAMS, Mutation Res., 13 (Iq7 I) 37 I, as well as dominant lethal mutations in nlature oocvtes (CATTANACH,lilt. J. Radial. Biol.. 3 (IQ5()) 288; (;EN[-ROSO el al., Mutation Res., I I (1971) 4tI. Therefore TEM was used to stud) the effect of a chemical mutagen on comparable germ cell stages in both sexes .primordial ,~.gonia and spernlatogonia--with the dominant lethal assay. An additional comparison of the TEM effect on primordial spermatogonia and adult spermatogonia was carried out by analyzing primary spermatocytes for the occurrence of recipr~mal translocation.~. IO- and I I - d a y old embryos were treated in utero with () different doses of TEM ranging from o.o5 to o.5 mg/kg. These animals were out-crossed for the dominant lethal assay at the age of IO-r2 weeks. No dominant lethal mutations were found fl,r either sex, but a pronounced cell killing effect was .bserved for b~,th primordial oogonia and spermatogonia. From IO males per dose treated in uh'ro 5oo-.Iooo primary spermatocytes per dose were analyzed. From IO nlales per dose treated as adults 5oo primary spermatocytes per dose were analyzed I2O days after treatment. In all, 5 translocation multivalents were observed among 470o diakinese.--metaphases I in the pre-natally treated experimental groups versus mine in 5oo cellb of the concurrent controls. This result is due to change (P -- o.6). In treated adult males a total of 11 translocation multivalents were found among 300 diakineses metaphases [ of ttle experilnental groups versus none in lOOO cells of the c
16 BUCKEL, U., Institut ffir Anthropologie und Humangenetik der Universitht Heidelberg, 69 Heidelberg I, Neuenheimerfeld 328 (West Germany).
Mutagenicity of Mysoline in spermatogenesis of mice Some anticonvulsant drugs have been shown to increase the frequency of chromosomal anomalies. The purpose of the present investigations was to determine whether one of the often-used anticonvulsant drugs--Mysoline- also increases the chromosomal damage in spermatogenesis of mice. As a screening systetn, we used the dominant lethal test and cytogenetic inve.~tigation of spermatogonia.
EUROPEAN ENVIRONMENTAL MUTAGEN SOCIETY
205
In the dominant lethal test system, male mice of the NMRI strain were treated with Mysoline at 35o and 7° mg/kg body weight and mated with untreated females over a period of 8 weeks. In the cytogenetic investigations, NMRI random-bred male mice were treated twice with 7o, 200, 350 and 612.5 mg Mysoline per kg body weight at 24-h intervals. Chromosome preparations were made 9.5, 15.5 and 23 h after the second application according to the method of Hoo AND BOWLES (1971). A z and NBU 2 were included to allow comparisons to be drawn in the cytogenetic test system. Mysoline induced a significant dominant lethality in the post-meiotic stages when applied in the lower dose. In spermatogonia, the test substance only slightly increased the frequency of chromosome aberrations.
17 M~OUTSCHEN-DAHMEN, J., M. MOUTSCHEN-DAHMEN, N. DEGRAEVE, N. HOUBRECHTS AND A. COLIZZI, Genetics Department, University of Li6ge (Belgium).
Genetical hazards of
aldehydes from
mouse experiments
It is well known that several aldehydes can be induced by irradiation of various media, which makes it important to study their genetical hazards. In the present studies, the toxicity of crotonaldehyde and butyraldehyde was investigated after i.p. injection of male mice of the Q strain. From the results, an acute dose (I rag/animal) was selected to investigate the effects on meiotic processes during a period of I month after injection. Chromosome damage was observed at all stages of spermatogenesis, but the sensitivity of each stage was different after each chemical. Special meiotic anomalies consisting of degenerative nuclei, multispindle cells and polyploid cells were observed after treatment at all spermatogenesis stages. The possible origins of these anomalies will be discussed. The effects of both aldehydes were also investigated after the mice had been given water containing one or the other (0.2 g/1 water each day for one month) and the effects at meiosis were followed for a 1-month period. Anomalies similar to those observed after acute i.p. injection occurred in about the same amount for both aldehydes although butyraldehyde showed less toxicity after acute doses. The bearing of these results on environmental mutagenesis will be discussed in relation to the amount of the compounds induced after irradiation of media.
18 RATHENBERG, R., Institut ftir Anthropologie und Humangenetik, University of
Heidelberg, Heidelberg (West Germany).
Comparative studies on spermatogonia of mice and Chinese hamsters after X - r a y t r e a t m e n t Spermatogonia of mammals would be valuable material for testing potential mutagens.
4TH ANNUAI.MEETING. HEIDELBERG
15 ADLER, I.-D., Abteilung ftir Genetik, Gesellschaft ffir Strahlen- und Umweltforschung, D-8o42 Neuherberg (W. Germany)
Primordial germ cell sensitivity to mutagenic effects of T E M Trietllylenemelainine (TEM) is known t o induce specific locus nmtations and translocations in mouse spermatogonia (CATTANACH, Mutation Res., 3 (r066) 346; CATTANACHAND WILLIAMS, Mutation Res., 13 (Iq7 I) 37 I, as well as dominant lethal mutations in nlature oocvtes (CATTANACH,lilt. J. Radial. Biol.. 3 (IQ5()) 288; (;EN[-ROSO el al., Mutation Res., I I (1971) 4tI. Therefore TEM was used to stud) the effect of a chemical mutagen on comparable germ cell stages in both sexes .primordial ,~.gonia and spernlatogonia--with the dominant lethal assay. An additional comparison of the TEM effect on primordial spermatogonia and adult spermatogonia was carried out by analyzing primary spermatocytes for the occurrence of recipr~mal translocation.~. IO- and I I - d a y old embryos were treated in utero with () different doses of TEM ranging from o.o5 to o.5 mg/kg. These animals were out-crossed for the dominant lethal assay at the age of IO-r2 weeks. No dominant lethal mutations were found fl,r either sex, but a pronounced cell killing effect was .bserved for b~,th primordial oogonia and spermatogonia. From IO males per dose treated in uh'ro 5oo-.Iooo primary spermatocytes per dose were analyzed. From IO nlales per dose treated as adults 5oo primary spermatocytes per dose were analyzed I2O days after treatment. In all, 5 translocation multivalents were observed among 470o diakinese.--metaphases I in the pre-natally treated experimental groups versus mine in 5oo cellb of the concurrent controls. This result is due to change (P -- o.6). In treated adult males a total of 11 translocation multivalents were found among 300 diakineses metaphases [ of ttle experilnental groups versus none in lOOO cells of the c
16 BUCKEL, U., Institut ffir Anthropologie und Humangenetik der Universitht Heidelberg, 69 Heidelberg I, Neuenheimerfeld 328 (West Germany).
Mutagenicity of Mysoline in spermatogenesis of mice Some anticonvulsant drugs have been shown to increase the frequency of chromosomal anomalies. The purpose of the present investigations was to determine whether one of the often-used anticonvulsant drugs--Mysoline- also increases the chromosomal damage in spermatogenesis of mice. As a screening systetn, we used the dominant lethal test and cytogenetic inve.~tigation of spermatogonia.
EUROPEAN ENVIRONMENTAL MUTAGEN SOCIETY
205
In the dominant lethal test system, male mice of the NMRI strain were treated with Mysoline at 35o and 7° mg/kg body weight and mated with untreated females over a period of 8 weeks. In the cytogenetic investigations, NMRI random-bred male mice were treated twice with 7o, 200, 350 and 612.5 mg Mysoline per kg body weight at 24-h intervals. Chromosome preparations were made 9.5, 15.5 and 23 h after the second application according to the method of Hoo AND BOWLES (1971). A z and NBU 2 were included to allow comparisons to be drawn in the cytogenetic test system. Mysoline induced a significant dominant lethality in the post-meiotic stages when applied in the lower dose. In spermatogonia, the test substance only slightly increased the frequency of chromosome aberrations.
17 M~OUTSCHEN-DAHMEN, J., M. MOUTSCHEN-DAHMEN, N. DEGRAEVE, N. HOUBRECHTS AND A. COLIZZI, Genetics Department, University of Li6ge (Belgium).
Genetical hazards of
aldehydes from
mouse experiments
It is well known that several aldehydes can be induced by irradiation of various media, which makes it important to study their genetical hazards. In the present studies, the toxicity of crotonaldehyde and butyraldehyde was investigated after i.p. injection of male mice of the Q strain. From the results, an acute dose (I rag/animal) was selected to investigate the effects on meiotic processes during a period of I month after injection. Chromosome damage was observed at all stages of spermatogenesis, but the sensitivity of each stage was different after each chemical. Special meiotic anomalies consisting of degenerative nuclei, multispindle cells and polyploid cells were observed after treatment at all spermatogenesis stages. The possible origins of these anomalies will be discussed. The effects of both aldehydes were also investigated after the mice had been given water containing one or the other (0.2 g/1 water each day for one month) and the effects at meiosis were followed for a 1-month period. Anomalies similar to those observed after acute i.p. injection occurred in about the same amount for both aldehydes although butyraldehyde showed less toxicity after acute doses. The bearing of these results on environmental mutagenesis will be discussed in relation to the amount of the compounds induced after irradiation of media.
18 RATHENBERG, R., Institut ftir Anthropologie und Humangenetik, University of
Heidelberg, Heidelberg (West Germany).
Comparative studies on spermatogonia of mice and Chinese hamsters after X - r a y t r e a t m e n t Spermatogonia of mammals would be valuable material for testing potential mutagens.