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PVC manufacturing area for 13 years. After evaluating 200 metaphases which had been scored for gaps, breaks,

fragments, dicentrics, rings, chromatid and chromosome translocations and dele- tions, an increased frequency of structural aberrations could be established.

73 Fleig, I., and A.M. Thiess, Arbeitsmedizin und Gesundheitsschutz, Aktiengesellschaft, 6700 Ludwigshafen (W. Germany)

BASF

Chromosome investigations of persons exposed to dimethylcarbamoyl chloride and diethylcarbamoyl chloride

In view of the proven mutagenic effect of DMCC and DECC in various bac- terial tests, a chromosome analysis was undertaken on: (a) 10 employees who had been exposed to these substances between 4 and 17 years; and (b) 10 con- trol persons similar in age to the exposed persons, but with no history of involvement with DMCC or DECC.

100 cells per individual were scored for gaps, breaks, fragments, dicentrics, rings, chromatid and chromosome translocations, and deletions.

There was a slight increase in the rate of aberrant metaphases in the exposed group but the statistical evaluation revealed no significant difference either incl. or excl. gaps compared with the control group.

With reference to the results we have given in our paper, it can be said that according to the exposure conditions under which the workers we examined were submitted, there is no evidence of chromosome damage as a result of exposure to DMCC or DECC.

74 Fox, Margaret, Paterson Laboratories, Christie Hospital, Manchester M20 9BX (U.K.)

Non-mutational origin of drug resistance after exposure of mammalian cells to purine analogues in vitro

Much of the observed variability of phenotypes in purine-analogue-resistant cell lines of mouse (L5178Y) and Chinese hamster (V79) can be at tr ibuted to alterations in cellular biochemistry induced by the selective drug and is of non- mutational origin. Permanently stable HGPRT- clones with some characteristics of structural gene mutants can be isolated from both cell types after exposure to single high doses of selective agents (surviving fraction 1 × 10-5). However, exposure to and selection of, clones at any sub-toxic concentrations and their subsequent maintenance under selective conditions allows survival of non- mutant, induced resistant phenotypes. Drug-induced phenotypic modification occurs rapidly on exposure (with 72 h), the clones are initially HAT*, show

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low-level resistance and are typically unstable when cultured in the absence of the selective drug. It is necessary, however, to culture these resistant variants for 100 cell generations or longer before the loss of resistance is manifest.

Thus, the common practices of maintaining resistant lines under low level selective pressure, of purging "wild-type" and "resistant" lines of accumulated forward mutants or "revertants" by short-term exposure to selective agents and of growing resistant lines for only a limited period (1--2 weeks) before pheno- typic characterisation is to be strongly discouraged as the subsequent results can be highly misleading. The implications of these findings in relation to the use of other antimetabolites as selective agents, the characterisation of the resultant resistant lines, and the interpretation of dose--response and expres- sion time data for a variety of selective agents will be discussed.

75 Fumero, S., and A. Mondino, Istituto di Ricerche Biomediche "A. Marxer", Ivrea (Italy) and R. Barale and N. Loprieno, Laboratorio di Genetics, Univer- sity of Pisa (Italy)

Mutagenicity of industrial compounds evaluated by means of yeast genetic systems

There are many chemical compounds of wide use in the chemical industry (solvents, halogenated hydrocarbons, aromatic polycyclic hydrocarbons, mono- mers employed in the resin and plastic industry) which have been shown to produce different genetic effects (reverse and forward mutations, gene-conver- sions and mitotic recombinations) on yeasts (S. cerevisiae and S. pombe). The use of yeasts, moreover, in the mutagenic analyses of such a class of com- pounds has resulted very appropriate in the study of the "in vitro" and "in vivo" metabolic conversion of the original compounds tested.

We will present data related to the mutagenic analyses of some other chemi- cals (trichloro ethylene and its epoxidic metabolite, epichlorohydrine) in com- parison with known chemical carcinogen: "in vivo" studies with host-mediated assay have provided data of extreme interest in the evaluation of the mutagenic activity of these compounds for a prediction of their possible cancerogenic activity.

Part of the work has been supported by Commiss ion of European Communities.

76 Gaulden, Mary Esther, V.P. Collins a and M.J. Hinton b , Department of Radio- logy, University of Texas Southwestern Medical School, Dallas, TX 75235, a Radiology Department, Rosewood Hospital, Houston, TX and b Office of Harris County District Attorney, Houston, TX 77002 (U.S.A.)

Cytogenetic studies of a boy criminally exposed to curie sources of cesium-137