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14 N. Loprieno, Laboratorio di Genetica dell'Universit~ and Laboratorio di Muta- genesi e Differenziamento del CNR, Pisa (Italy)

Occupational hazards: mutagenic activity of industrial compounds

Since many years the induction of somatic chromosomal mutations in indivi- duals exposed to toxic compounds in the working environment has been exten- sively documented: among others, several metals and organic solvents have been shown to produce a variety of biological effects on chromosomes (breaks, translocations, rings, etc.).

The employment of simple biological test organisms, such as microbial cells, or complex organisms easy to handle, such as Drosophila in the programs for the evaluation or screening of the genetic effects induced by chemicals of industrial use has allowed a more appropriate experimental definition of genetic hazards for workers.

During recent years, moreover, it has been demonstrated that some cellular steps of the mutational pathway are in common with the cancerogenic process and that suitable methodologies may evidentiate in a predictive way the pos- sible cancerogenic activity of a given compound. Several chemicals known to produce cancer in professionally exposed individuals, have been also found to be mutagenic after being tested with these new analytical procedures.

Examples are given by 4-aminobiphenyl, benzidine, /3-naphthylamine vinyl chloride, bis-chloromethyl ether. It is therefore possible to predict an extensive use of these methodological investigations in the future, in order to provide greater sefety and an improved quality of life in the working environment.

In the present paper genetic effects observed in laboratory test organisms by industrial compounds to which professional individuals are exposed are pres- ented and discussed.

15 Helmut Bartsch, International Agency for Research on Cancer, Lyon (France) and Nicola Loprieno, Laboratorio di Mutagenesi e Differenziamento, CNR, Pisa (Italy)

Vinyl chloride (VCM): an example for evaluating adverse biological effects in short-term tests

The various adverse biological effects of vinyl chloride (VCM), a recognized carcinogen in animals and man, appear to be largely dependent upon its metab- olic conversion into chemically reactive metabolites.

In a collaborative study with various research institutes *, the biological activity of VCM, 3 of its identified mammalian metabolites (chloroethylene oxide, chloroacetaldehyde and chloroacetic acid) and a putative metabolic

* A. Croisy, Gif -sur-Yvet te , France ; E. H u b e r m a n , R e h o v o t , Israel; H.F. Stich, R.H.C. San, Van- couver , Canada ; E. Vogel, Le iden , The Nether lands ; and F. Zadjela, Orsay, France .

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intermediate, 2-chloroethanol, were assayed in several prescreening tests for carcinogens, namely: (a) assay for electrophilic reactivity; (b) tissue-mediated mutagenicity tests with Salmonella typhimurium or with (c) S. pombe and S. cerevisiae; (d) host-mediated assay in mice with S. pombe; (e) in vitro muta- genicity in Chinese hamster V79 cells using ouabain or 8-azaguanine resistance; (f) induction of DNA repair synthesis ("unscheduled" incorporation of [3HI thymidine) in cultured human fibroblasts and (g) tests for recessive lethal muta- tions in Drosophila melanogaster.

Chloroethylene oxide, which was the most active compound in the assay sys- tems (a) to (f), induced local tumours in mice upon repeated subcutaneous administration. These results strongly support the hypothesis that chloro- ethylene oxide is one of the principal mutagenic and/or carcinogenic inter- mediates formed from VCM by mammalian metabolism. By comparing quan- titatively the data available from the literature and unpublished results with VCM and its derivatives, the sensitivity and limitations of the individual assay systems will be discussed.

16 N.P. Bochkov, Institute of Medical Genetics, AMS USSR, Moscow (U.S.S.R.)

Monitoring of human populations in connection with environmental pollution: chromosomal aberrations

The study of the mutat ion process in human populations during some period of time permits to understand the causes of this process and to make prognoses of the frequency of hereditary diseases. The rate of progress of science and technology, unknown before, may greatly influence the genetic structure of human populations and change the intensity of the mutat ion process. There- fore, the control over the level of the mutat ion process in man is one of the most urgent tasks in modern genetics. The basis of such a control is the know- ledge of all its primary laws. Information is necessary on the average mutat ion rate, the range of fluctuations, and their dependence upon different factors.

Literary data do not permit to draw conclusions on all the questions. Sum- marizing of the data is possible only in those cases when they are obtained by correct methods. The characteristics of spontaneous chromosome and genome mutat ion rates in human germ cells are given on the basis of cytogenetic investi- gations of newborns, infants with congenital malformations, and spontaneous abortions. The calculations of the confidence interval based on the mutat ion rate show the size of samples necessary for registration of mutagenic effects of different intensity. The range of fluctuations of these samples is wide. Thus, a twofold increase of the frequency of chromosome diseases may be registered when 1400 newborns have been investigated, and to estimate a 20% increase it is necessary to investigate 90,000 persons.

On the basis of literary data it is possible to determine the possibilities of monitoring generalized populations and groups being in closer contact with mutagens. Such calculations are made for the control over the spontaneous mutat ion process in somatic cells.