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Chromosomal aberrations and anticonvulsant drugs
EUROPEAN ENVIRONMENTALMUTAGEN
SOCIETY
35
22 GROSSE, K.-P., G. SCHWANITZ, H.-D. ROTT AND H. F. WISSM~~LLER, Humangenetik und Anthropologie der Universitat Erlangen-Ntirnberg, sitats-Kinderklinik der Universitat Erlangen-Niirnberg (W. Germany).
Chromosomal
aberrations
and anticonvulsant
Institut fur und Univer-
drugs
A group of 32 women, suffering from epilepsy and treated with anticonvulsant and their children (aged o to 3 years) who had been exposed to these drugs pregnancy, were examined for chromosomal changes. These women and their children showed significantly higher aberration rates (9 < 0.001) in comparison with an untreated control group. A difference in type and quantity of induced chromosomal aberrations between the various groups of anticonvulsant drugs could not be ascertained because of the great variety of drug combinations taken by the mothers. We found, however, a significant correlation, demonstrable for several types of aberration, between the aberration rate of the mothers and their respective children. Thus by analysing the chromosomes of probands on anticonvulsive monotherapy, it should be possible to state whether there are anticonvulsant drugs with a minor clastogenic effect. drugs, during
23 HANSMANN, I., AND G. R~HRBORN, University of Heidelberg, Heidelberg
Stage sensitivity
Institute of Anthropology (W. Germany)
in the oogenesis
and Human
Genetics,
of mice
The stage sensitivity in the oogenesis of mice was investigated by transplacental treatment of embryonic oogonia and cells at meiotic prophase I. After birth we treated the early and late dictyotene stage as well as the preovulatory (metaphase I) and the ovulatory phases (anaphase I, telophase I, metaphase II) The analysis was made in the unfertilized ovulated metaphase II oocyte according to the method of R~HRRORN AND HAKSMANN (Hv,mangenetik, 13 (1971) 184-198). As test substances we used both the folic acid antagonist methotrexate and the alkylating agents cyclophosphamide (Cytoxan) and z,3,5-triethyleneiminobenzoquinone-I,4 (Trenimon). Embryonic oogonia as well as the preovulatory phase of adult females proved to be the most sensitive to the induction of chromosomal aberrations analysed in the unfertilized oocytes. The least sensitive stages were the embryonic prophase and the early dictyotene, the latter stage showing strong cytotoxic effects after treatment. Furthermore, the simultaneous occurrence of transplacentally induced mutations and teratogenic effects was observed in both male and female embryos. Animals with teratogenic damage that had survived birth and reached sexual maturity showed increased rates of chromosomal aberrations in oocytes and in spermatogonial cells.
SOCIETY
35
22 GROSSE, K.-P., G. SCHWANITZ, H.-D. ROTT AND H. F. WISSM~~LLER, Humangenetik und Anthropologie der Universitat Erlangen-Ntirnberg, sitats-Kinderklinik der Universitat Erlangen-Niirnberg (W. Germany).
Chromosomal
aberrations
and anticonvulsant
Institut fur und Univer-
drugs
A group of 32 women, suffering from epilepsy and treated with anticonvulsant and their children (aged o to 3 years) who had been exposed to these drugs pregnancy, were examined for chromosomal changes. These women and their children showed significantly higher aberration rates (9 < 0.001) in comparison with an untreated control group. A difference in type and quantity of induced chromosomal aberrations between the various groups of anticonvulsant drugs could not be ascertained because of the great variety of drug combinations taken by the mothers. We found, however, a significant correlation, demonstrable for several types of aberration, between the aberration rate of the mothers and their respective children. Thus by analysing the chromosomes of probands on anticonvulsive monotherapy, it should be possible to state whether there are anticonvulsant drugs with a minor clastogenic effect. drugs, during
23 HANSMANN, I., AND G. R~HRBORN, University of Heidelberg, Heidelberg
Stage sensitivity
Institute of Anthropology (W. Germany)
in the oogenesis
and Human
Genetics,
of mice
The stage sensitivity in the oogenesis of mice was investigated by transplacental treatment of embryonic oogonia and cells at meiotic prophase I. After birth we treated the early and late dictyotene stage as well as the preovulatory (metaphase I) and the ovulatory phases (anaphase I, telophase I, metaphase II) The analysis was made in the unfertilized ovulated metaphase II oocyte according to the method of R~HRRORN AND HAKSMANN (Hv,mangenetik, 13 (1971) 184-198). As test substances we used both the folic acid antagonist methotrexate and the alkylating agents cyclophosphamide (Cytoxan) and z,3,5-triethyleneiminobenzoquinone-I,4 (Trenimon). Embryonic oogonia as well as the preovulatory phase of adult females proved to be the most sensitive to the induction of chromosomal aberrations analysed in the unfertilized oocytes. The least sensitive stages were the embryonic prophase and the early dictyotene, the latter stage showing strong cytotoxic effects after treatment. Furthermore, the simultaneous occurrence of transplacentally induced mutations and teratogenic effects was observed in both male and female embryos. Animals with teratogenic damage that had survived birth and reached sexual maturity showed increased rates of chromosomal aberrations in oocytes and in spermatogonial cells.