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Induction of dominant lethals by fractionated doses of EMS
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gain information on the basic biochemical and developmental aspects of teratogenesis. In a second series of experiments designed to investigate gene-teratogen interactions, 3 wild-type strains of Drosophila (Canton S, Canton $109 and Oregon R) were used to test 9 commonly used drugs. All 3 strains identified cortisone, hydrocortisone, sulfanilamide, and pentobarbital as nonteratogens. In the 5 suspected teratogens (diphenylhydantoin, diethyl-stilbestrol, testosterone, imipramine, and tolbutamide), dose--response differences were found between the 3 strains. These results suggest that the Drosophila assay might be capable of identifying teratogens by their effect on neuron and muscle differentiation. Sensitive strains might be used to study mechanisms of abnormal development and gene involvement in teratogenic resistance.
Favor, J., School of Biology, Georgia Institute of Technology, Atlanta, GA
(U.S.A.) Induction of dominant lethals by fractionated doses of EMS The induction of dominant lethals by chemical mutagens involves the interaction of the mutagen with DNA and the transformation of the DNA lesions to dominant lethals. The shouldered dose--response curve of ethyl methanesulfonate induced dominant lethals suggests either a non-linear relation between dose of EMS and DNA lesion production, or a limited repair system capable of repairing most DNA lesions at lower doses. The analysis of the induction of dominant lethals by fractionated doses of mutagen may provide information about these processes. Male DBA/2J mice were injected on 3 consecutive days with the following mg EMS/kg doses: 0, 0, 0; 225, 0, 0; 112.5, 112.5, 0; 112.5, 0, 112.5; 50, 175, 0; and 175, 50, 0. Males were mated to DBA/2J females following the third treatment for 12 days. Thus, data represent treated late spermatid and spermatozoa. The per cent dominant lethals in the 6 treatment groups were. resp. 0, 63, 21, 32, 32 and 43. Initial analyses indicate that fractionation of a dose of mutagen produces intermediate effects. The data were further compared to expected frequencies of dominant lethals under the assumptions of (a) complete additivity o f induced dominant lethals of the fractionated doses, in which case the expected,frequency of dominant lethals was calculated as the sum o f induced dominant,lethals for each single dose, or (b) completely dependent on the maximum dose to which the DNA was exposed, which was calculated as the sum of the residual dose of EMS from the first treatment and the secor~d treatment dose. The results indicate that the data differ significantly from expected induced dominant lethal frequencies under both assumptions and suggest that a repair system with limited capability may be operating. Present address: I n s t i t u t flit Genetik, GSF, D-S042 Neuherberg, F.R.G.
gain information on the basic biochemical and developmental aspects of teratogenesis. In a second series of experiments designed to investigate gene-teratogen interactions, 3 wild-type strains of Drosophila (Canton S, Canton $109 and Oregon R) were used to test 9 commonly used drugs. All 3 strains identified cortisone, hydrocortisone, sulfanilamide, and pentobarbital as nonteratogens. In the 5 suspected teratogens (diphenylhydantoin, diethyl-stilbestrol, testosterone, imipramine, and tolbutamide), dose--response differences were found between the 3 strains. These results suggest that the Drosophila assay might be capable of identifying teratogens by their effect on neuron and muscle differentiation. Sensitive strains might be used to study mechanisms of abnormal development and gene involvement in teratogenic resistance.
Favor, J., School of Biology, Georgia Institute of Technology, Atlanta, GA
(U.S.A.) Induction of dominant lethals by fractionated doses of EMS The induction of dominant lethals by chemical mutagens involves the interaction of the mutagen with DNA and the transformation of the DNA lesions to dominant lethals. The shouldered dose--response curve of ethyl methanesulfonate induced dominant lethals suggests either a non-linear relation between dose of EMS and DNA lesion production, or a limited repair system capable of repairing most DNA lesions at lower doses. The analysis of the induction of dominant lethals by fractionated doses of mutagen may provide information about these processes. Male DBA/2J mice were injected on 3 consecutive days with the following mg EMS/kg doses: 0, 0, 0; 225, 0, 0; 112.5, 112.5, 0; 112.5, 0, 112.5; 50, 175, 0; and 175, 50, 0. Males were mated to DBA/2J females following the third treatment for 12 days. Thus, data represent treated late spermatid and spermatozoa. The per cent dominant lethals in the 6 treatment groups were. resp. 0, 63, 21, 32, 32 and 43. Initial analyses indicate that fractionation of a dose of mutagen produces intermediate effects. The data were further compared to expected frequencies of dominant lethals under the assumptions of (a) complete additivity o f induced dominant lethals of the fractionated doses, in which case the expected,frequency of dominant lethals was calculated as the sum o f induced dominant,lethals for each single dose, or (b) completely dependent on the maximum dose to which the DNA was exposed, which was calculated as the sum of the residual dose of EMS from the first treatment and the secor~d treatment dose. The results indicate that the data differ significantly from expected induced dominant lethal frequencies under both assumptions and suggest that a repair system with limited capability may be operating. Present address: I n s t i t u t flit Genetik, GSF, D-S042 Neuherberg, F.R.G.