Search PubMed⌕ Search

Biomedical subjects

E Gocke

Publications and source records attributed to E Gocke.

50 records · Page 3Linked to original sources

Mutagenicity of cosmetics ingredients licensed by the European Communities.

As part of our investigation into mutagenic effects of environmental compounds, we studied chemicals allowed as ingredients of cosmetics according to the guidelines of the Council of the European Communities (27 July 1976). We used three systems, the Salmonella/microsome test, the Basc test on Drosophila and the micronucleus test on mouse bone marrow. Of the 31 chemicals tested, 15 were mutagenic in the Ames test; and of these, 5 were also mutagenic in the Basc test and 2 in the micronucleus test.

Animals↗

Mutagenicity study of Remsen-Fahlberg saccharin and contaminants.

Saccharin and contaminants of commercial Remsen-Fahlberg saccharin were studied for mutagenic potential with the use of the Salmonella/microsome test, Basc-test in Drosophila melanogaster and micronucleus test in mice. In none of these tests were mutagenic effects of saccharin observed. Likewise, the ortho- and para-sulfamoylbenzoic acids (OSBA and PSBA) were ineffective. Para-toluenesulfonamide (PTS) and the major contaminant ortho-toluene-sulfonamide (OTS) exhibited weak mutagenic effects in a modified Salmonella/microsome test and in Drosophila. These results do not indicate mutagenic and therewith correlated carcinogenic potential of saccharin, but they emphasize the possible activity of contaminants.

Animals↗

Synthesis of inducible enzymes in irradiated yeast cells: inhibition by ionizing radiation.

The induced activity of the enzyme arginase was measured in diploid wild type Saccharomyces cerevisiae after X-ray and 241Am-alpha-particle exposure. It was found that after doses which are comparable to those necessary to reduce survival, little effect on enzyme activity is seen immediately after irradiation but it is reduced on further incubation. In this case there is an oxygen enhancement ratio of about 2 as for survival. Suppression immediately after exposure requires considerably higher doses, and no oxygen effect is seen. To achieve the same effect with alpha-particles requires even higher doses, the apparent r.b.e. is about 0 . 1. X-ray damage to induced enzyme activity is subject to liquid holding recovery. The results are discussed in relation to current theories of gene inactivation by ionizing radiation.

Alpha Particles↗

Effect of lucanthone (miracil D) on transcription of ribosomal RNA genes from Tetrahymena in vivo and in vitro.

Addition of lucanthone (1-5 mug/ml) to cultures of Tetrahymena results in a preferential inhibition of the synthesis of ribosomal RNA. Transcriptional studies with isolated nucleoli from Tetrahymena demonstrate that the endogenous RNA polymerases of the r-chromatin (chromatin form of rDNA) do not recognize the normal termination and move into the spacer region distal to the terminator in the presence of lucanthone. This is shown by hybridization of the transcript synthesized in the presence of the drug to restriction fragments of rDNA. Lucanthone seems specific in its action on termination as it does not inhibit the elongation process on the chromatin. Among various DNA-binding drugs tested only lucanthone and proflavine are found to cause repression of the termination. The data obtained suggest that the reduced synthesis of rRNA in lucanthone-treated eukaryotic cells is due to lack of reinitiating RNA polymerases possibly caused by improper termination.

Animals↗

Mutagenicity studies with x-ray-contrast media, analgesics, antipyretics, antirheumatics and some other pharmaceutical drugs in bacterial, Drosophila and mammalian test systems.

As part of our investigation into mutagenic effects of environmental compounds, we studied 21 pharmaceuticals most frequently sold in West Germany: 6 X-ray-contrast media, 13 analgesics, antipyretics and antirheumatics, 1 central stimulant, and 1 antidepressant. They were studied in different bacterial, Drosophila and mammalian test systems. 4 of these 21 compounds could be detected as mutagens in one of the test systems. namely: 1,2-dichloroethane induced an increase in the frequency of recessive sex-linked lethal mutations in Drosophila melanogaster, quinine dihydrochloride and dimethylaminophenazone were mutagenic in the Salmonella typhimurium tester strain TA98 in the presence of S-9 liver fraction derived from Aroclor-induced rats, and trilithium citrate caused a significant effect in the micronucleus test on bone marrow of NMRI mice.

Analgesics↗

The CAN1 locus of Saccharomyces cerevisiae: fine-structure analysis and forward mutation rates.

A system of strains and growth media was developed to allow efficient detection of forward mutation, reversion, complementation, and suppression at the canavanine-resistance (CAN1) locus of Saccharomyces cerevisiae. Genetic fine-structure analysis revealed that the map length is at least 40, and possibly as much as 60 X-ray map units; this is the longest gene map yet reported in S. cerevisiae. Allelic complementation was not observed, despite testing of a large number of allele pairs, and alleles suppressible by the ochre suppressor SUP11 were absent from a sample of 48 spontaneous mutants and occurred infrequently (7%) among a sample of ultraviolet-induced mutants. Infrequent mutant types included canavanine-resistant mutants capable of arginine uptake and alleles thought to represent deletions or inversions. In contrast to previous reports in the literature, the spontaneous forward mutation rate at CAN1 did not increase during meiosis.

Alleles↗

Expression of radiation-induced mutations at the arginine permease (CAN1) locus in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the expression of resistance to the L-arginine analog, L-canavanine, after mutagenesis, is strongly dependent on the metabolic state of the cell. The frequency of mutations recovered after exposure to ultraviolet light or X rays was measured under a variety of culture conditions. The results indicate that the frequency of mutants recovered is determined by the following three factors: (1) The potential mutants still possess enough permease activity to take up some of the cell poison, and some are therefore killed before they can express the mutant genotype. The sensitivity is strongly influenced by the endogenous free arginine, which is in turn influenced by the growth medium. (2) The rapid decay of the permease molecules and the inability of the potential mutants to resynthesize this protein results in a rapidly increasing change of expression when selection is delayed. (3) During the time when the permease activity is decaying, repair of the mutagen-induced damage appears to occur.

Arginine↗

Synthesis of inducible enzymes in irradiated yeast: UV effects on regulation and activity per cell.

The synthesis of two inducible enzymes in UV irradiated cells was determined during an 8 h postirradiation incubatin. In contrast to the reduction of synthesis shortly after irradiation the effect after a longer period of incubation depends on the radiation sensitivity of the strain. Since exposure inhibits division leading to different cell number in controls and irradiated samples the data are also analysed on a per cell basis. ta considerable increase of the activity per cell was observed. A maximum is reached at the end of the division delay.

Arginase↗

Transcriptional properties of nucleoli isolated from Tetrahymena.

Nucleoli can be isolated from Tetrahymena in a yield of 30-60%. The isolated nucleoli contain rDNA (at least 90% pure) and have a protein to DNA ratio of 30:1. The endogenous RNA-polymerase activity of the r-chromatin has the following properties: (i) The in vitro transcript has a maximal size identical to the in vivo 35S rRNA precursor, demonstrating correct termination on the gene, (ii) 79% of the in vitro transcript is complementary to cDNA of 17S and 25S rRNA which is close to the theoretical maximum for the 35S rRNA precursor, (iii) the elongation rate of the endogenous RNA-polymerase molecules is 9-12 nucleotides/sec, (iv) an average of 4-16 active RNA polymerases are associated with each rDNA molecule depending upon the preparation.

Animals↗

Synthesis of inducible enzymes in irradiated yeast cells. Ultraviolet effects on transcription and the influence of recovery processes.

The induced synthesis of arginase was measured in several yeast strains after ultraviolet light irradiation. There was an exponential dose-related reduction which was the same in all cell lines tested. This sensitivity is compatible with the size of the arginase structural gene if it is assumed that one pyrimidine dimer suffices for blocking transcription. The ultraviolet-induced synthesis inhibition is susceptible to photoreactivation and liquid holding recovery. The latter process is absent in a rad2 mutant and reduced in a rad9 mutant.

Arginase↗

Differential mutagenic activity of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) in Salmonella typhimurium strains in vitro and in vivo, in Drosophila, and in mice.

IQ, a heterocyclic aromatic amine which is formed during the frying of meat, was prepared by chemical synthesis. Its genotoxic potential was studied in bacteria, Drosophila and in mice. A mutagenic effect of IQ (frameshift induction) was detected in Salmonella typhimurium in experiments without metabolic activation; this effect was several orders of magnitude lower than that observed in the presence of an activation system. Ames tests with liver-homogenate S9 fraction from PCB-induced mice and rats confirmed the high mutagenic potency of IQ metabolites (Kasai et al., 1980a). Comparative studies on diagnostic Salmonella strains revealed that the high frameshift-inducing activity is independent of the plasmid pkM101; it is, however, greatly reduced by an intact excision-repair system for DNA lesions. The mutagenic activity of the metabolite(s) formed in vitro by S9 mix has a half-life of ca. 14 min. In the fruit fly, Drosophila melanogaster, IQ induced when used at sublethal concentrations, X-chromosomal recessive lethal mutations in male germ cells in a dose-dependent manner. In mice, tests were performed to detect somatic mutations: chromosomal anomalies (micronuclei) in bone marrow, and gene mutations (affecting coat pigmentation) in mice exposed to IQ in utero. No genotoxic effects were observed in these assays. However, the formation of mutagenic metabolites in the liver of IQ-treated mice was unequivocally demonstrated in host-mediated assays using Salmonella as mutagen probes in mice. The data demonstrate genotoxic activity of IQ in prokaryotic and eukaryotic organisms. The possible reasons for the different response of mammalian systems in vivo and the Salmonella system are discussed.

Animals↗