a study of the mutagenicity of thiram in mammalian cells in vitro

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245 point mutations and the system of the same fungus based upon its parasexual cycle for somatic recombination. In the Ames test the herbicides were tested at concentrations of 10, 100, 250, 500, 750 and 1000/~g/plate. 2,4-D and MCPA showed a weak mutagenic activity at 250, 500 and 750 #g/plate with $9 mix in the TA97 strain. At concentrations around 10 #g/ml which reduced the viability of conidia of A. nidulans to about 15% there was not any increase in the meth suppressor mutations. 2,4-D and MCPA had a low effect in the colony growth of A. nidulans even at the concentration of 1000 pg/ml, whereas 2,4-DB had a 50% reduction in growth at 60 #g/ml. There were indications that MCPA together with microsomes had a low recombinogenic effect in A. nidulans. This work was supported by the EEC, Grant No. ENV-561-GR(B). II.3B.4 Savkovi6, N., J. Pe~evski, D. Alavanti6 and D. Radivojevi6, Institute of Nuclear Sciences 'Boris Kidri~', Laboratory of Radiobiology, Belgrade (Yugoslavia) Genetic and cytogenetic effects induced in mice by commercial mixture of herbicides The aim of these studies was to examine whether commercial mixture, stomp + prometryn, herbicides have an effect on the reproductive system of mice. The mixture stomp + prometryn is a new product of the chemical industry 'Zorka'. In agriculture stomp + prometryn herbicides applied alone have shown excellent effects inhibiting development of weeds. For detection of possible genetic and cytogenetic effects the following test systems were applied: chromosomal aberrations; dominant lethal assays; mouse sperm abnormalities and the morphological changes in two successive generations. Male mice were treated with the mixture stomp + prometryn for 5 successive days by gavage at a dose of 1.250 mg/kg per day. Immediately upon the treatment each male was mated with 2 untreated females. The females were removed after 7 days. The obtained results indicated that stomp + prometryn did not show any effect on fertility and on induction of DL mutation. The frequency of sperm abnormalities was not higher than in the controls. No chromosomal translocations were found in the stage of diakinesis. Also, no morphological changes were found in the offspring in the first generation. In the second generation only 3 offspring from 190 had changes on the hair. II.3B.5 Zdzienicka, M.Z. 1, M. Zielehska 2; W. Vogel 3 and J.W.I.M. Simons 1, 1Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden (The Netherlands), 2 Department of Biochemistry, Warsaw Medical School, Poland, and 3 Abteilung Klinische Genetik der Universit~it Ulm (F.R.G.) A study of the mutagenicity of thiram in mammalian cells in vitro Thiram (CAS No. 137-26-8) is a widely used fungicide. It has been shown that thiram induces mutations in the Salmonella-microsome assay, in Aspergillus nidulans (Zdzienicka et al., 1979, 1981), and also has an effect on mammals interfering with normal differentiation of the germ cells by producing a significant increase of sperm abnormalities (Zdzienicka et al., 1982). In the present studies the effect of thiram on mammalian cells in vitro was examined. The ability of thiram to induce mutations and sister-chromatid

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point mutations and the system of the same fungus based upon its parasexual cycle for somatic recombination. In the Ames test the herbicides were tested at concentrations of 10, 100, 250, 500, 750 and 1000/~g/plate. 2,4-D and MCPA showed a weak mutagenic activity at 250, 500 and 750 #g /p la te with $9 mix in the TA97 strain. At concentrations around 10 # g / m l which reduced the viability of conidia of A. nidulans to about 15% there was not any increase in the meth suppressor mutations. 2,4-D and MCPA had a low effect in the colony growth of A. nidulans even at the concentration of 1000 pg /ml , whereas 2,4-DB had a 50% reduction in growth at 60 #g /ml . There were indications that MCPA together with microsomes had a low recombinogenic effect in A. nidulans.

This work was supported by the EEC, Grant No. ENV-561-GR (B).

II.3B.4

Savkovi6, N., J. Pe~evski, D. Alavanti6 and D. Radivojevi6, Institute of Nuclear Sciences 'Boris Kidri~', Laboratory of Radiobiology, Belgrade (Yugoslavia)

Genetic and cytogenetic effects induced in mice by commercial mixture of herbicides

The aim of these studies was to examine whether commercial mixture, stomp + prometryn, herbicides have an effect on the reproductive system of mice. The mixture stomp + prometryn is a new product of the chemical industry 'Zorka' . In agriculture stomp + prometryn herbicides applied alone have shown excellent effects inhibiting development of weeds. For detection of possible genetic and cytogenetic effects the following test systems were applied: chromosomal aberrations; dominant lethal assays; mouse sperm abnormalities and the morphological changes in two successive generations. Male mice were treated with the mixture stomp + prometryn for 5 successive days by gavage at a dose of 1.250 mg/kg per day. Immediately upon the treatment each male was mated with 2 untreated females. The females were removed after 7 days. The obtained results indicated that stomp + prometryn did not show any effect on fertility and on induction of DL mutation. The frequency of sperm abnormalities was not higher than in the controls. No chromosomal translocations were found in the stage of diakinesis. Also, no morphological changes were found in the offspring in the first generation. In the second generation only 3 offspring from 190 had changes on the hair.

II.3B.5

Zdzienicka, M.Z. 1, M. Zielehska 2; W. Vogel 3 and J.W.I.M. Simons 1, 1Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden (The Netherlands), 2 Department of Biochemistry, Warsaw Medical School, Poland, and 3 Abteilung Klinische Genetik der Universit~it Ulm (F.R.G.)

A study of the mutagenicity of thiram in mammalian cells in vitro

Thiram (CAS No. 137-26-8) is a widely used fungicide. It has been shown that thiram induces mutations in the Salmonella-microsome assay, in Aspergillus nidulans (Zdzienicka et al., 1979, 1981), and also has an effect on mammals interfering with normal differentiation of the germ cells by producing a significant increase of sperm abnormalities (Zdzienicka et al., 1982). In the present studies the effect of thiram on mammalian cells in vitro was examined. The ability of thiram to induce mutations and sister-chromatid

246

exchanges (SCE) was investigated in Chinese hamster cells with and without metabolic activation ($9 mix). Thiram at the concentrations 10-7-5 x 10 -7 M did not induce mutations in Oua or H G P R T loci in CHO cells although at the highest concentrations, a strong killing effect was observed. In the same range of concentrations thiram induced a dose-dependent increase in SCE frequencies in V79 cells. An almost 3-fold increase in SCE level above the number in control cells was observed after thiram (5 x 10 -7 M) treatment. No differences were seen when $9 mix was included. At the same concentration thiram induced a 2-fold increase in SCEs in human lymphocytes in vitro. The results indicate that exposure to thiram could involve a genetic risk and further studies should be pursued.

II.3C.1

Benigni, R., A. Calcagnile, A. Giuliani, P. Leopardi, F. Degrassi, C. Tanzarella, R. Ricordy, F. Palitti and A. Paoletti, Istituto Superiore di Sanith, Centro di Genetica Evoluzionistica CNR, Universith Cattolica, Rome (Italy)

Cytogenetic damage and DNA-repair studies in lymphocytes of rubber industry workers

The in vivo levels of chromosomal aberrations and SCEs were monitored in a group of 34 vulcanizers; the UV-induced UDS capacity was also studied in lymphocytes belonging to the same blood samples. The control group (16 persons) was matched both for age and smoking. When the UDS responses of the two groups were compared, a significant decrease in the ability to repair the UV-induced D N A damage among the vulcanizers was observed. The frequency of SCEs and aberrations in the two populations did not show any appreciable difference; a positive correlation was found between SCE levels and cigarette smoking.

This research was partially supported by the E.E.C. (Contract No. 030 ENV I (s); project leader A. Carere).

II.3C.2

Del Carratore, R., E. Cundari, C. Morganti, C. Bauer, C. Corsi, R. Nieri, M. Paolini and G. Bronzetti, Istituto di Mutagenesi e Differenziamento CNR, Via Svezia, 10, 1-56100 Pisa (Italy)

Mutagenicity of complex mixtures used in tannery industries

This work is part of an interdisciplinary research program involving the construction of risk maps delimiting the zone of increased tumor incidence in the 'Comprensorio del Cuoio' (leather industry area near Florence). Our effort concentrated not only on well-known active molecules, but also on complex mixtures, as they occur in the environment, containing a wide variety of compounds capable of causing antagonistic and synergistic biological effects. For this reason, 28 commercial products used in the tannery industries were tested using the Salmonella typhimurium and Saccharomyces cerevisiae mammalian micro- some mutagenicity tests.

5 samples were found to be mutagenic; of them Chromitan B and MS containing Cr 3+ are involved in the tanning process and resulted positive principally on strains TA1535 and TA100 in the presence of metabolic activation.

Erhavit A, a limiting agent, showed activity on strain TA1535. Bruno and Rosso Avival used in the dyeing of leather showed a considerable genetic effect on strains TA98 and TA1537 and on strain D7 of S. cereoisiae both in presence and in absence of metabolic activation.