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Cytotoxic, clastogenic and morphological transforming effects of chromic oxide on mammalian cells in vitro
186 1.3.1 Elias, Z., O. Schneider, O. Poirot, M.C. Dani~re and F. Aubry, I.N.R.S., 54501 Vandoeuvre (France) Cytotoxic, clastogenic and morphological transforming effects of chromic oxide on mammalian cells in vitro
An insoluble compound of trivalent chromium (Cr 3+), chromic oxide (Cr203), has been tested in vitro for its effect on cell-cycle progression and cell survival, for its ability to increase the frequency of sister-chromatid exchanges (SCEs) and chromosomal aberrations in V79 cells and to induce morphological transformation in Syrian hamster embryo cells (HEC). The presence of phagocytosed Cr203 particles in the cytoplasm of treated cells was confirmed by electron microscopy. A progressive decrease of the cell fraction in S phase and an increase in G~ and above all in G2-M fractions in the first 6 h of treatment with concentrations of 25-100/~g of Cr203 per ml was observed by measuring DNA histograms with flow cytometry. In the cells exposed for 24-48 h, a delay in the cell cycle, and increases in SCEs and chromosomal aberrations, all concentration-dependent, were found. In the HEC bioassay, Cr203 induced, after 8 days of exposure, the formation of morphologically transformed colonies. The data suggest specific biological actions of this C r 3+ compound.
1.3.2 Fahrig, R., Fraunhofer-Institut fi~r Toxikologie und Aerosolforschung, Stadtfelddamm 35, D-3000 Hannover (F.R.G.) Genetic mode of action of cocarcinogens and tumor promoters in yeast and mice
In experiments with yeast strain MP1, cocarcinogens were found to be comutagenic and antirecombinogenic, and tumor promoters to be corecombinogenic and antimutagenic. Substances being cocarcinogens as well as tumor promoters had an intermediary effect. These results were confirmed in the mammalian spot test. In this test system the antimutagen limonene reduced the effect of ENU from 17% animals with color spots (325 F1 animals scored for color spots) down to 14% (797 F1 animals scored for color spots), the comutagen catechol enhanced the effect up to 21% (469 F~ animals scored for color spots). Furthermore, the yield of light brown spots (presumed products of gene mutations and small deletions) was clearly lower in the ENU/limonene group (7%) than in the ENU/catechol group (18%) and the yield of near-white and wild-type black spots (presumed products of reciprocal recombination) was clearly higher (14% against 4%). Twin spots being the strongest evidence for appearance of reciprocal recombination due to mitotic crossing-over, were observed in the ENU/limonene group only. The workwith yeast has been supportedby the 'Deutsche Forschungsgemeinschaft',the work with miceby the 'Bundesministerium for Forschungund Technologie(CMT44)'.
An insoluble compound of trivalent chromium (Cr 3+), chromic oxide (Cr203), has been tested in vitro for its effect on cell-cycle progression and cell survival, for its ability to increase the frequency of sister-chromatid exchanges (SCEs) and chromosomal aberrations in V79 cells and to induce morphological transformation in Syrian hamster embryo cells (HEC). The presence of phagocytosed Cr203 particles in the cytoplasm of treated cells was confirmed by electron microscopy. A progressive decrease of the cell fraction in S phase and an increase in G~ and above all in G2-M fractions in the first 6 h of treatment with concentrations of 25-100/~g of Cr203 per ml was observed by measuring DNA histograms with flow cytometry. In the cells exposed for 24-48 h, a delay in the cell cycle, and increases in SCEs and chromosomal aberrations, all concentration-dependent, were found. In the HEC bioassay, Cr203 induced, after 8 days of exposure, the formation of morphologically transformed colonies. The data suggest specific biological actions of this C r 3+ compound.
1.3.2 Fahrig, R., Fraunhofer-Institut fi~r Toxikologie und Aerosolforschung, Stadtfelddamm 35, D-3000 Hannover (F.R.G.) Genetic mode of action of cocarcinogens and tumor promoters in yeast and mice
In experiments with yeast strain MP1, cocarcinogens were found to be comutagenic and antirecombinogenic, and tumor promoters to be corecombinogenic and antimutagenic. Substances being cocarcinogens as well as tumor promoters had an intermediary effect. These results were confirmed in the mammalian spot test. In this test system the antimutagen limonene reduced the effect of ENU from 17% animals with color spots (325 F1 animals scored for color spots) down to 14% (797 F1 animals scored for color spots), the comutagen catechol enhanced the effect up to 21% (469 F~ animals scored for color spots). Furthermore, the yield of light brown spots (presumed products of gene mutations and small deletions) was clearly lower in the ENU/limonene group (7%) than in the ENU/catechol group (18%) and the yield of near-white and wild-type black spots (presumed products of reciprocal recombination) was clearly higher (14% against 4%). Twin spots being the strongest evidence for appearance of reciprocal recombination due to mitotic crossing-over, were observed in the ENU/limonene group only. The workwith yeast has been supportedby the 'Deutsche Forschungsgemeinschaft',the work with miceby the 'Bundesministerium for Forschungund Technologie(CMT44)'.