Mutagenic effect of heavy metal salts on Salmonella in activation systems in vivo and in vitro

223 Mutat. Res. 20, 1, 1973; Popowska and Janion, Biochem. Biophys. Res. Comm. 56, 459, 1974}, and that of N6OH2AP reported briefly (Janion, Acta Biochim. Polon. 23, 57, 1976). Mutagenic activity of 5 meN4OHdCyd is now presented. The synthesis, and a study of the mutagenic properties of 5meN4OHdCyd, was undertaken to compare the effectiveness of ribo- and deoxyribo-nucleoside analogs. The lack of deoxycytidine kinase in both bacterial strains made impossible tests of the N4OHCyd, N4OHdCyd series. Both N4OHCyd and N6OH2AP show wide spectra of mutagenic action. Six of the seven markers tested were revertible by these analogs. 5 meN4OHdCyd seems to act more specifically. Only a few mutations were induced to revert. There was a distinct difference in behaviour between 2AP and 5meN4OHdCyd. Some mutations were revertible by 5meN4OHdCyd, but not by 2AP. It is possible that 5meN 4 OHdCyd leads mainly to CG--TA transitions. Among the tested compounds the most potent mutagen was N6OH2AP. In some cases it gave more than 1000 revertants per plate. The further order (decreasing) of mutagenic potency was as follows: N4OHCyd > 2AP > 5MeN 4OHCyd. None of the mutations tested was revertible by BUdR, when estimated by the plate test. The introduction of additional thy mutations did not increase the detectability of BUdR reversions. S u p p o r t e d b y t h e Polish A c a d e m y of Sciences (Project 09.7.1.1.4.1.)

48 L.M. Kalinina and G.H. Polukhina, Institute of General Genetics, USSR Acad e m y of Science Moscow (U.S.S.R.) Mutagenic effect of heavy metal salts on Salmonella in activation systems in vivo and in vitro Heavy metal salts play an important part in the rapidly growing environmental pollution by industrial products and wastes. Cadmium and zinc belong to this group and are known to participate in metabolic processes since their ions are present in vitally important enzymes. On chronic exposure, these metals can accumulate in mammalian tissues causing various toxic reactions. The communication presents data on the relative mutagenic effects of cadmium and zinc chloride on indicator Salmonella strains developed by Ames. The mutagenic activity of the compounds was estimated according to their ability to induce reversions from histidine a u x o t r o p h y to prototrophy. Different methods of mutagenic activity estimation using salmonella strains have been compared. Routine microbiological testing did not reveal any significant mutagenic activity of the compounds. Cadmium chloride showed little activity in in vitro metabolic activation system while zinc chloride exhibited a significant mutagenic effect. The effect was species-specific with respect to liver homogenates of different mammals used in this system (mice, rats, humans). The highest mutagenic effect of zonc chloride was observed with mouse liver homogenates. The genetic design of sensitive Salmonella strains enabled us to

224 identify the types of mutational alterations induced by the heavy metal in DNA: cadmium chloride induced base pair substitutions while exposure to zinc chloride resulted in frame shift mutations.

49 A. Kappas, Biology Dept., Nuclear Research Centre "Democritus", Athens (Greece) Genetic

effects of fungicides through me'~abolic activation in Aspergillus

nidulans A number of fungicides which were previously found not to affect the genetic stability of Aspergillus nidulans heterozygous diploid strains were tested again in the same system by using the metabolic activation technique. Microsomal preparations from rats together with proper cofactors were added into the culture medium with or without the fungitoxicants. Scoring for colour sectors showed that one of the tested fungicides namely Daconil (Tetrachloroisophthalonitrile) a member of the aromatic hydrocarbon group increased the somatic segregation of the diploid strain of the fungus by a factor 6. It is interesting to note that this fungicide was the only one out of a number of the aromatic hydrocarbons tested previously w i t h o u t microsomes which did not show any effect in Aspergillus (Phytopathology, 66 (1976) 217--220).

50 J. Kirfily, A. Czeizel and I. Szentesi, Budapest Chemical Works and National Institute of Hygiene, Budapest (Hungary) Genetic study o n workers producing organophosphate insecticides Organic phosphorous insecticides may cause human chromosome mutations in persons with severe acute intoxication. In order to obtain data on the genetic effect of prolonged occupational exposure to small doses a study was initiated on workers producing and formulating organic phosphorous insecticides in the Budapest Chemical Works. On the one hand the chromosomes of O-control (49 persons), industrial control (14 persons), positive control (tetrachlorobenzene, 25 persons) and three organophosphate insecticide groups (Trichlorofon, 17 persons; Diazinon, 34 persons; Imidan, 25 persons) were studied in peripheral blood cultures. The frequency of chromatid-type aberrations in all organophosphate groups was higher than in that of controls. Occurrence of stable chromosome-type aberrations was higher in the Diazinon group. On the other hand a genetic-epidemiologic survey has been made of nearly 2000 workers. Evaluation of data is in process.