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20 N. Degraeve, J. Moutschen, M. Moutschen-Dahmen, J. Gilot-Delhalle~ N. Houbrechts and A. Colizzi, Laboratory of Genetics, University of Liege (Belgium)

Cytogenetic and genetic effects of Phosan-plus

Phosan-plus, a mixture of three insecticides: methoxychlor and two organo- phosphates dimethoate and malathion, was tested in male mice after one single I.P. injection (30 mg/kg).

Cytological damage was analyzed in bone marrow during the first three days after injection and in testis, at intervals ranging from 12 h to 44 days.

Slight chromosome breakage was observed in spermatogonia especially after 24 and 48 h.

However, the chromosome damage did not result in increased frequency of sperm anomalies at 40 to 44 days after injection. Observation of diakinesis from 11 to 16 days did not reveal significant cytological damage.

Tests on bone marrow, namely frequency of polychromatic erythrocyte micronuclei and chromosome breakage, were not significant during the first three days after injection.

Dominant lethals were investigated for testing the sensitivity of pre-, post- and meiotic stages. No enhancement over the control was observed.

The effects of Phosan-plus were also analyzed in relation with its toxicity after t reatment of Schizosaccharomyces pombe, strain ade 7-C8, There was no increase of the number of revertants with and without addition of microsomal fraction.

Our results are in general agreement with data of the literature obtained with the compounds tested individually.

The bearings of these results for human hazards will be discussed.

21 John Ashby, D. Paton, J.A. Styles, Diana Anderson and E. Longstaff, Christie Hospital, Manchester (U.K.)

The use of the S. typhimurium mutat ion assay and cell transformation in vitro as short-term carcinogen tests to monitor the structural inactivation of known carcinogens and to detect potential carcinogenicity in new compounds

An evaluation of six short-term carcinogen tests using fifty-eight known human or animal carcinogens and sixty-two putative non-carcinogens has been undertaken recently in our laboratory and reported elsewhere. Two of these tests, namely the S. typhimurium mutat ion assay and mammalian cell transfor- mation in vitro, both of which incorporate metabolic activation, showed a greater than 90% correlation between test response and long-term animal data, and they thus offer a useful method of studying the chemical structure/biolog- ical activity relationships of chemical carcinogens.

The results of several such structure/activity studies will be described. These

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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