EUROPEAN ENVIRONMENTALMUTAGEN SOCIETY
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duals in which it occurs, and the damage could result in oncogenic or teratogenic processes. For a better definition of this risk, we treated mammalian cells, both in vitro and in vivo with substances having a known mitoclastic action, thus revealing the establishment of processes of polyploidization-segregation and mitotic instability.
11 RUZICSKA, P., S. PI~TER AND A. CZEIZEL, Laboratory of Human Genetics, National Institute of Public Health, Budapest (Hungary).
Studies on the chromosomal mutagenic effect of Benomyl in rats and humans Pregnant female rats of the inbred R Amsterdam and Long Evans strains were treated per os with single daily doses of 200 mg and more Benomyl between the 7th and I2th days of pregnancy. Benomyl treatment was highly teratogenic for the F~ generation, resulting primarily in a high frequency of skeletal malformations and a high rate of foetal mortality with resorption. Chromosome studies performed on the Fz foetuses removed from the treated pregnant females and grown in cell cultures for 7 days also revealed chromosomal mutagenic effects as shown by the increased frequency of chromosome aberrations (both stable and unstable) and by the presence of somatic exchange figures. On the other hand, chromosome studies performed on the bone marrow of the same pregnant females failed to yield any evidence for chromosomal mutation. Chromosome studies on the blood cultures of 20 workers engaged in the production of Benomyl showed no increased frequency of structural chromosome aberrations.
12 SCOTT, D., M. Fox AND B. W. FOX, Paterson Laboratories, Christie Hospital and
Holt Radium Institute, Withington, Manchester M2o 9BX (England).
Differential induction of chromosome aberrations in mammalian cell lines In order to investigate the factors which control the susceptibility of mammalian chromosomes to the induction of structural aberrations we have utilised pairs of cell lines with pronounced differential sensitivities to killing with various agents, because these cell lines also show large differences in amounts of induced chromosome damage. For example, a pair of cultured Yoshida lymphosarcoma cell lines differentially sensitive to killing with sulphur mustard (and methylene dimethane sulphonate and ultraviolet light) also differ markedly in levels of induced chromosome damage. This is in spite of equal alkylation of DNA, RNA and protein of the sensitive and resistant lines. The correlation between chromosome damage and cell killing suggests a causal relationship. The difference in susceptibility to chromosome damage in the sensitive and resistant cell lines cannot be explained by difference in chromosome number since
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modal numbers and karyotypes are similar. Neither is there any difference in anlount> of DNA repair replication after treatment of the two cell lines with sulphur mustard. Lesions that give rise to chromosoinal aberrations inav be different from, or represent only a small proportion of, those that elicit repair replication. Other repair (or lnisrepair) processes m a y be involved in aberration formation. Tile same pair of Yoshida cell lines showed equal survival, chromosome damage and DNA repair replication after X-irradiation.
13 STEGNER, [., AND A. HERWIG, Institut ftir Anthropologie und Humangenetik der Universit~it Heidelberg, 69 Heidelberg I, Neuenheimer Feld 328 (West-Germany).
Comparative mutagenicity test of three cyclophosphamides in the bone ma rrow of Chinese hamsters ( Cricetulus griseus) During two experimental set-ups, dose dependency and time dependency of induced chromosomal aberrations were tested after i.p. application of three cyclophosphamides. The substances analysed in the bone marrow of Chinese hamsters were Cytoxan, Trofosfamide and Isofosfanfide. Two applications were made with an interval of 24 tl. The bone marrow was prepared 6, I2, 24 and 48 h after tile second application. Doses of I/3O, 3/3 o and 9/30 of LDs0 were used. With cytoxan a linear dose-dependency was observed. Concerning time dependency we observed that tile mutation rate decreased to the control level within 48 1,. This work was sponsored by the Deutsche Forschungsgemeinschaft.
201
duals in which it occurs, and the damage could result in oncogenic or teratogenic processes. For a better definition of this risk, we treated mammalian cells, both in vitro and in vivo with substances having a known mitoclastic action, thus revealing the establishment of processes of polyploidization-segregation and mitotic instability.
11 RUZICSKA, P., S. PI~TER AND A. CZEIZEL, Laboratory of Human Genetics, National Institute of Public Health, Budapest (Hungary).
Studies on the chromosomal mutagenic effect of Benomyl in rats and humans Pregnant female rats of the inbred R Amsterdam and Long Evans strains were treated per os with single daily doses of 200 mg and more Benomyl between the 7th and I2th days of pregnancy. Benomyl treatment was highly teratogenic for the F~ generation, resulting primarily in a high frequency of skeletal malformations and a high rate of foetal mortality with resorption. Chromosome studies performed on the Fz foetuses removed from the treated pregnant females and grown in cell cultures for 7 days also revealed chromosomal mutagenic effects as shown by the increased frequency of chromosome aberrations (both stable and unstable) and by the presence of somatic exchange figures. On the other hand, chromosome studies performed on the bone marrow of the same pregnant females failed to yield any evidence for chromosomal mutation. Chromosome studies on the blood cultures of 20 workers engaged in the production of Benomyl showed no increased frequency of structural chromosome aberrations.
12 SCOTT, D., M. Fox AND B. W. FOX, Paterson Laboratories, Christie Hospital and
Holt Radium Institute, Withington, Manchester M2o 9BX (England).
Differential induction of chromosome aberrations in mammalian cell lines In order to investigate the factors which control the susceptibility of mammalian chromosomes to the induction of structural aberrations we have utilised pairs of cell lines with pronounced differential sensitivities to killing with various agents, because these cell lines also show large differences in amounts of induced chromosome damage. For example, a pair of cultured Yoshida lymphosarcoma cell lines differentially sensitive to killing with sulphur mustard (and methylene dimethane sulphonate and ultraviolet light) also differ markedly in levels of induced chromosome damage. This is in spite of equal alkylation of DNA, RNA and protein of the sensitive and resistant lines. The correlation between chromosome damage and cell killing suggests a causal relationship. The difference in susceptibility to chromosome damage in the sensitive and resistant cell lines cannot be explained by difference in chromosome number since
202
4TH ANNUAL MEETING, HEIDELBERG
modal numbers and karyotypes are similar. Neither is there any difference in anlount> of DNA repair replication after treatment of the two cell lines with sulphur mustard. Lesions that give rise to chromosoinal aberrations inav be different from, or represent only a small proportion of, those that elicit repair replication. Other repair (or lnisrepair) processes m a y be involved in aberration formation. Tile same pair of Yoshida cell lines showed equal survival, chromosome damage and DNA repair replication after X-irradiation.
13 STEGNER, [., AND A. HERWIG, Institut ftir Anthropologie und Humangenetik der Universit~it Heidelberg, 69 Heidelberg I, Neuenheimer Feld 328 (West-Germany).
Comparative mutagenicity test of three cyclophosphamides in the bone ma rrow of Chinese hamsters ( Cricetulus griseus) During two experimental set-ups, dose dependency and time dependency of induced chromosomal aberrations were tested after i.p. application of three cyclophosphamides. The substances analysed in the bone marrow of Chinese hamsters were Cytoxan, Trofosfamide and Isofosfanfide. Two applications were made with an interval of 24 tl. The bone marrow was prepared 6, I2, 24 and 48 h after tile second application. Doses of I/3O, 3/3 o and 9/30 of LDs0 were used. With cytoxan a linear dose-dependency was observed. Concerning time dependency we observed that tile mutation rate decreased to the control level within 48 1,. This work was sponsored by the Deutsche Forschungsgemeinschaft.
