use of sister chromatic exchange techniques for cytological detection of mutagen carcinogen exposure

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205 will include the effect produced by isosteric replacement of the benzene rings of known carcinogens such as benzidine with heteroaromatic rings, and the inactivating effect produced by ortho-dimethyl group across a wide range of arylamine carcinogens such as benzidine, 4-NQO and 3-methyl-4-nitropyridine- N-oxide. In addition, the results obtained for a wide range of saccharin deriv- atives will be discussed. 22 Paul Perry, MRC Clinical and Population Cytogenetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU (U.K.) Use of sister chromatic exchange techniques for cytological detection of muta- gen carcinogen exposure A series of experiments on the induction of sister chromatid exchange (SCE) in cultured Chinese hamster ovary cells, exposed to physical and chemical mutagens in various stages of the cell cycle, have yielded information on the sensitivity of cells to exchange induction and on the mechanisms whereby these exchanges are produced. The frequency of SCE is vastly increased by most of the mutagens/carcino- gens tested at dose levels which induce relatively few chromosomal aberrations. Some of the chemicals showed a comparative inability to induce SCEs in vitro e.g. cyclophosphamide and dimethylbenzanthracene, because they require metabolism in vivo to a more active metabolite. Experiments have been performed utilising the metabolising ability of cultured BHK cells and mouse embryo cells, and significant increases in SCE obtained in vitro for both these chemicals. Increases in SCE have also been observed in blood lymphocytes of patients exposed to cytotoxic drugs. The results of these experiments will be presented and discussed. 23 T. Kuroki, C. Drevon and R. Montesano, International Agency for Research on Cancer, Lyon (France) Microsome-mediated mitagenesis of a Chinese hamster cell line by nitrosamines A microsome-mediated mutagenesis system for mammalian cells has been established using V79 cells, a Chinese hamster cell line. The cells, grown in monolayer, were treated with nitrosamines in the presence of a post-mitochon- drial fraction ($15) and co-factors for one hour, washed and incubated for 2 to 3 h in fresh culture medium and then the cells were plated for toxicity and mutagenicity assays. Mutation was determined by resistance to 20 pg/ml 8-aza- guanine. In our assay system, S15 and co-factors were found not to be toxic to the cells. Dose-related mutation and cytotoxicity were induced after incubation with dimethylnitrosamine (DMN) only in the presence of both the S15 fraction of the livers of BD-VI rats and the co-factors. Pre-treatment of the rats with

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205

will include the effect produced by isosteric replacement of the benzene rings of known carcinogens such as benzidine with heteroaromatic rings, and the inactivating effect produced by ortho-dimethyl group across a wide range of arylamine carcinogens such as benzidine, 4-NQO and 3-methyl-4-nitropyridine- N-oxide. In addition, the results obtained for a wide range of saccharin deriv- atives will be discussed.

22 Paul Perry, MRC Clinical and Population Cytogenetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU (U.K.)

Use of sister chromatic exchange techniques for cytological detect ion of muta- gen carcinogen exposure

A series of experiments on the induction of sister chromatid exchange (SCE) in cultured Chinese hamster ovary cells, exposed to physical and chemical mutagens in various stages of the cell cycle, have yielded information on the sensitivity of cells to exchange induction and on the mechanisms whereby these exchanges are produced.

The frequency of SCE is vastly increased by most of the mutagens/carcino- gens tested at dose levels which induce relatively few chromosomal aberrations. Some of the chemicals showed a comparative inability to induce SCEs in vitro e.g. cyclophosphamide and dimethylbenzanthracene, because they require metabolism in vivo to a more active metabolite. Experiments have been performed utilising the metabolising ability of cultured BHK cells and mouse embryo cells, and significant increases in SCE obtained in vitro for both these chemicals. Increases in SCE have also been observed in blood lymphocytes of patients exposed to cytotoxic drugs. The results of these experiments will be presented and discussed.

23 T. Kuroki, C. Drevon and R. Montesano, International Agency for Research on Cancer, Lyon (France)

Microsome-mediated mitagenesis of a Chinese hamster cell line by nitrosamines

A microsome-mediated mutagenesis system for mammalian cells has been established using V79 cells, a Chinese hamster cell line. The cells, grown in monolayer, were treated with nitrosamines in the presence of a post-mitochon- drial fraction ($15) and co-factors for one hour, washed and incubated for 2 to 3 h in fresh culture medium and then the cells were plated for toxicity and mutagenicity assays. Mutation was determined by resistance to 20 pg/ml 8-aza- guanine. In our assay system, S15 and co-factors were found not to be toxic to the cells. Dose-related mutat ion and cytotoxic i ty were induced after incubation with dimethylnitrosamine (DMN) only in the presence of both the S15 fraction of the livers of BD-VI rats and the co-factors. Pre-treatment of the rats with