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The chromosome changes as the consequence of action of some chemotherapeutics in malignant diseases
226 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (CNU-ethanol) having one chloroethyl group and 1,3-bis(2-chloroethyl)-3-nitrosourea (BCNU) with two chloroethyl groups were tested in spermatozoa of Drosophila, in mouse lymphoma cells (L5178Y) in vitro, and in bone marrow and spermatogonial cells of mice. In Drosophila, both chemicals induced sex-linked recessive lethals, dominant lethals, total and partial loss of sex-chromosomes, and autosomal translocations. There was no difference between both compounds in the types of genetic damage produced. When comparing the mutagenic effectiveness of equimolar concentrations (1 mM), BCNU induced 10 times more genetic damage than CNU-ethanol. In mouse l y m p h o m a cells in vitro, however, in which the induction of HGPRT-deficiency was scored (as measured by 6-thioguanine resistance), both compounds were equally mutagenic at equimolar concentrations (10-2--5.10 -2 mM). Moreover the same cell toxicity was observed. In the mouse, the induction of micronuclei in erythrocytes of the bone marrow, chromosome aberrations in bone marrow cells as well as in spermatogonial cells was studied at equal doses (dose range 0.36--81.45 mg/kg) of CNU-ethanol and BCNU. At some concentrations CNU-ethanol was equally effective as BCNU. At other concentrations CNU-ethanol was approximately 2--5 times more active than BCNU. In conclusion, it is obvious that the results obtained with the various test systems are markedly different. Since there are no a priori reasons to assume that the two compounds would react differently with the DNA in the various test systems secondary factors presumably can be held responsible for the observed differences. T h i s w o r k w a s s u p p o r t e d b y t h e D u t c h M i n i s t r y o f P u b l i c H e a l t h a n d E n v i r o n m e n t a l H y g i e n e , by P H S Research Grant No. ESO 1 0 2 7 - - 0 2 from the National Institute of E n v i r o n m e n t a l Health Sciences (U.S.A.) •a n d b y c o n t r a c t N o . C 3 0 - 7 4 - 1 E N V N b e t w e e n t h e E E C and t h e S t a t e U n i v e r s i t y o f L e i d e n .
53 B. Krajin~ani6, Z. Zuni6, A. Lazarov and V. Veljkovi6, Faculty of Defectology, University of Belgrade, Radiobiological Laboratory, Boris Kidrich Institute, Medical Military Academy and Laboratory for Theoretical Physics, Boris Kidrich Institute, Belgrade (Yugoslavia) The c h r o m o s o m e changes as the consequence of action of some chemotherapeutics in malignant diseases
On the basis of theoretical prediction of mutagenecity induced by chemical compounds experimental investigations of effects of two preselected cytostatics have been undertaken. The patients suffering from Myelosis chr. (10), Morhus Hodgkin (8) and Lymphosarcoma (2} were treated with the therapeutic doses of " V e l b e " and "Myleran" during a period of 6 months. In agreement with the theory experimental findings have proved the existence
227 of expected chromosomal deformations. All groups of patients treated with " V e l b e " and "Myleran" showed in groups G and C monosomia, trisomia, cell endoreduplications and cells with extra-long chromosomes and fragments.
54 Roza Kubiak, Institute of Systematic and Experimental Academy of Sciences, Cracow (Poland)
Zoology, Polish
The effect of aflatoxins on Chinese hamster cells in culture In view of the great interest in problems of mutagenicity and carcinogenicity of aflatoxins one more study has been undertaken to investigate their effect on Chinese hamster cells in primary cultures. The experiments were performed with four different aflatoxins (AF): B~, B2, G~ and G2. The solutions were prepared from crystal form by dissolving in 1% DMSO. The hamster cells were exposed to various concentrations of each kind of aflatoxin: 100, 50, 20, 10 and 5 pg/ml of final concentration. The primary cultures originated from lung, heart and kidney of male Chinese hamster. The cells were subcultured the day before treatment. The fixation of cells was done immediately after 4 and 24 h of continuous treatment and also after 24 h of recovery. Air-dried preparations were stained with orcein as well as by C- and G-banding techniques. For each treatment metaphases as well as anaphases were analyzed for chromosomal aberrations. A significant increase in the number of abnormal anaphases was observed at the higher concentrations of aflatoxin used. Those abnormalities consisted of lagging chromosomes, fragments, stickiness and bridges. The analysis of metaphases showed many gaps and breaks, mostly of the chromatid type. The breaks were distributed nonrandomly among chromosomes and among chromosome regions. Most of breaks were localized in the largest chromosomes as well as in X and Y chromosomes. It seems also to be corresponding to the heterochromatic regions of those chromosomes. The treatment with the highest concentration of AFB1 caused the strongest effect as reflected in partial pulverization of chromosomes. The comparison of the effects of four aflatoxins used had also been made.
55 M. Ku6erov~ and V.S. Zhurkov, Genetic Laboratory, Institute of Hygiene and Epidemiology, Prague Pediatric Department, Postgraduate Medical Institute, Prague (C.S.S.R.) Institute of Medical Genetics, Academy of Medical Sciences, Moscow (U.S.S.R.) Population cytogenetic study of mutagenic effect of epichlorohydrin Peripheral lymphocytes of 35 workers occupationally exposed to high doses of epichlorohydrin (ECHH) were cytogenetically analysed. Blood samples were collected in three time intervals: (1) before exposure as a control, (2) after one-
53 B. Krajin~ani6, Z. Zuni6, A. Lazarov and V. Veljkovi6, Faculty of Defectology, University of Belgrade, Radiobiological Laboratory, Boris Kidrich Institute, Medical Military Academy and Laboratory for Theoretical Physics, Boris Kidrich Institute, Belgrade (Yugoslavia) The c h r o m o s o m e changes as the consequence of action of some chemotherapeutics in malignant diseases
On the basis of theoretical prediction of mutagenecity induced by chemical compounds experimental investigations of effects of two preselected cytostatics have been undertaken. The patients suffering from Myelosis chr. (10), Morhus Hodgkin (8) and Lymphosarcoma (2} were treated with the therapeutic doses of " V e l b e " and "Myleran" during a period of 6 months. In agreement with the theory experimental findings have proved the existence
227 of expected chromosomal deformations. All groups of patients treated with " V e l b e " and "Myleran" showed in groups G and C monosomia, trisomia, cell endoreduplications and cells with extra-long chromosomes and fragments.
54 Roza Kubiak, Institute of Systematic and Experimental Academy of Sciences, Cracow (Poland)
Zoology, Polish
The effect of aflatoxins on Chinese hamster cells in culture In view of the great interest in problems of mutagenicity and carcinogenicity of aflatoxins one more study has been undertaken to investigate their effect on Chinese hamster cells in primary cultures. The experiments were performed with four different aflatoxins (AF): B~, B2, G~ and G2. The solutions were prepared from crystal form by dissolving in 1% DMSO. The hamster cells were exposed to various concentrations of each kind of aflatoxin: 100, 50, 20, 10 and 5 pg/ml of final concentration. The primary cultures originated from lung, heart and kidney of male Chinese hamster. The cells were subcultured the day before treatment. The fixation of cells was done immediately after 4 and 24 h of continuous treatment and also after 24 h of recovery. Air-dried preparations were stained with orcein as well as by C- and G-banding techniques. For each treatment metaphases as well as anaphases were analyzed for chromosomal aberrations. A significant increase in the number of abnormal anaphases was observed at the higher concentrations of aflatoxin used. Those abnormalities consisted of lagging chromosomes, fragments, stickiness and bridges. The analysis of metaphases showed many gaps and breaks, mostly of the chromatid type. The breaks were distributed nonrandomly among chromosomes and among chromosome regions. Most of breaks were localized in the largest chromosomes as well as in X and Y chromosomes. It seems also to be corresponding to the heterochromatic regions of those chromosomes. The treatment with the highest concentration of AFB1 caused the strongest effect as reflected in partial pulverization of chromosomes. The comparison of the effects of four aflatoxins used had also been made.
55 M. Ku6erov~ and V.S. Zhurkov, Genetic Laboratory, Institute of Hygiene and Epidemiology, Prague Pediatric Department, Postgraduate Medical Institute, Prague (C.S.S.R.) Institute of Medical Genetics, Academy of Medical Sciences, Moscow (U.S.S.R.) Population cytogenetic study of mutagenic effect of epichlorohydrin Peripheral lymphocytes of 35 workers occupationally exposed to high doses of epichlorohydrin (ECHH) were cytogenetically analysed. Blood samples were collected in three time intervals: (1) before exposure as a control, (2) after one-