Short-term tests for transplacentally active carcinogens: I. Micronucleus formation in fetal and maternal mouse erythroblasts |
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Authors: | R.J. Cole Natalie Taylor Jane Cole C.F. Arlett |
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Affiliation: | 1. Developmental Genetics Laboratory, School of Biological Sciences, Great Britain;2. Biology Division, Sussex Centre for Medical Research, Great Britain;3. MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton Great Britain |
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Abstract: | A cell-kinetic model for the application of the micronucleus test to polychromatic erythrocytes in mouse fetal liver, fetal blood, and maternal bone marrow after exposure to clastogenic agents is described. The time of expression and dose-response relationships obtained with γ-radiation, methyl methanesulphonate, procarbazine, mitomycin C and benzo[a]pyrene are analysed in terms of this model. The numbers of target cells damaged per unit dose has been calculated and the dose equivalents obtained. Maternal and fetal cells show similar sensitivity to γ-radiation, but fetal cells are markedly more sensitive to MMS and procarbazine. This probably due to differences in tissue distribution and metabolism. Maternal and fetal erythroid tissues can show linear and exponential dose-response relationships, which may not coincide (e.g. with MMS). It is concluded that risks from fetal exposure to genotoxic agents cannot be reliably predicted from in vivo tests restricted to adult animals. However, the micronucleus technique appled to fetal erythroid cells proveds a rapid and reliable short-term test, appropriate to minimising risks of genome damage during prenatal development. |
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Keywords: | DMSO dimethyl sulphoxide FCS fetal calf serum HBSS Hank s balanced salt solution i.p. intra-perotoneal MMS methyl methanesulphonate Mito C mitomycin C PC procarbazine PCE polychromatic erythrocyte TELo (mutation) toxic dose low, (lowest dose reported to produce mutagenic effect) |
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