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D Harnasch

Publications and source records attributed to D Harnasch.

9 recordsLinked to original sources
PubMed1986

Chemical structure and mutagenic activity of aminoimidazoquinolines and aminonaphthimidazoles related to 2-amino-3-methylimidazo[4,5-f]quinoline.

We have synthesized 11 heterocyclic aromatic amines with chemical structures related to that of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), a potent mutagen occurring in broiled sardines, fried beef and beef extract. The mutagenic activity of these IQ analogs was studied and compared with that of IQ using the Ames test with strain TA98 of Salmonella typhimurium in presence of a metabolic activation system (S9 mix) derived from rat liver. The mutagenic activities of the IQ analogs vary over a million-fold; structure-activity comparisons indicate major contributions of the methyl substitution in the imidazole ring and of the quinoline-N, and significant contributions of methylation of the exocyclic amino group and of the geometry of the entire ring system.

Animals↗
PubMed1984

Studies on the induction of histocompatibility gene mutations in germ cells of mice by chemical mutagens and/or virus-inducing compounds.

This work continues earlier studies concerning the use of histocompatibility mutations in mammalian germ cells as a mutagenicity test system (H test). The rate of spontaneous H mutations was re-examined using a new basis for the classification of H mutants. This procedure led to very high frequencies of suspected spontaneous H mutants: among C57Bl/6 mice, 6% and among C3H mice, 9%. F2 hybrids of a cross between these strains revealed 1% suspected H mutants. Using the same procedure, the sensitivity of the H test was examined with the mutagens ethylnitrosourea, benzo[a]pyrene, 2-acetylaminofluorene (2-AAF), with the solvent dimethyl sulfoxide (DMSO) and with the antibacterial nitrofurantoin. It was possible to demonstrate the mutagenic potential of all mutagens tested as well as their specific action on the different stages of male germ cell development. We succeeded in demonstrating the mutagenicity of 2-AAF for the first time in germ cells of a mammal. In contrast to the negative result with benzopyrene (BP) in the specific locus test, BP induced H mutants even at the very low dose of 2 mg/kg. DMSO was found to induce H mutations in spermatogonia. This extraordinary result is possibly due to the virus-inducing properties of this compound. Nitrofurantoin which is often used in treating bacterial infections of the urinary tract in humans showed a very stage-specific action on maturing spermatids. The value of the H test for mutagenicity testing is discussed with respect to its sensitivity and economy. The very high spontaneous frequency of suspected H mutants and the ease of inducing increased mutant frequencies by mutagens and by DMSO suggest the possibility that the majority of the histoincompatibilities found in the H test are due to induced antigenic gene products of endogenous viruses. This, however, does not interfere with the applicability of the H test for mutagenicity testing, but rather seems to augment its sensitivity to alkylating mutagens as well as mutagens which probably cause frameshift mutations. Other tests for mutations and/or inherited tumor proneness using mouse germ cells can easily be combined with the H test, because the test animal does not have to be killed, thus reducing the cost of the test.

2-Acetylaminofluorene↗
PubMed1983

Genotoxicity study of CS (ortho-chlorobenzylidenemalononitrile) in Salmonella, Drosophila, and mice. Failure to detect mutagenic effects.

The lacrimatory agent CS was examined for genotoxic properties. In vitro, Salmonella typhimurium was exposed to CS at concentrations up to 1.5 mg per plate and reverse mutations were assayed. In vivo: male Drosophilae were fed with CS and sex-linked recessive lethal mutations in sperm cells were assayed using the Basc test. Further, mice were exposed to CS by oral or intraperitoneal administration; bone marrow erythrocytes were analysed for chromosomal mutations by means of the micronucleus test. All experiments failed to show a mutagenic activity of CS.

Animals↗
PubMed1982

Histocompatibility gene mutation rates, spontaneous and induced by the chemical mutagen procarbazine.

The use of histocompatibility mutations in mice for the development of a mutagenicity test has been proposed by several immunologists. The aim of our work was to find a basis for the establishment of the H-test as a mutagenicity test. We therefore determined the spontaneous mutation rates of H-genes in the two inbred mouse strains C3H and C57Bl. Furthermore, we tried to increase the mutation rate by the well-known chemical mutagen procarbazine. The spontaneous mutation rates of H-genes of both strains were identical at about 1.2 x 10(-3). After long-term mutagen treatment with 100 mg procarbazine/kg per week, the mutant frequency increased to about 7% and decreased again when the total dose had reached more than 9 x 100 mg/kg in C57Bl mice and more than 14 x 100 mg/kg in C3H mice. These results are discussed in comparison with procarbazine experiments with other mutagenicity test systems. The feasibility of the H-test for mutagenicity testing remains to be verified by further experiments with other germ-line mutagens.

Animals↗
PubMed1981

Origin of life between Scylla and Charybdis.

The "package model" discussed here is concerned with the preservation of genetic information by primordial compartments. Each viable "package" encloses a complete set of unlinked genes in varying numbers of copies. Due to stochastic distribution and error-prone replication two potent perils endanger the informational integrity of packages: fluctuation and mutation. A computer simulation was used to quantify the effects of fluctuation, mutation, and package death by accident. Assuming reasonable rates for these parameters it is suggested that life started out with compartments containing not more than 3 different genes.

Biological Evolution↗
PubMed1979

A rapid method for preimmunisation and grafting of mice with ear skin.

A schedule for a histocompatibility test among mice involving preimmunisation with ear skin is described and has been tested with the weak transplantation antigen H-Y in C57BL responder and C3H nonresponder strains. The transplantation technique was tested by autografting, and more than 99% of the operations were successful. The priming method reduces the survival of ear skin grafts in every combination tested.

Animals↗
PubMedDate not supplied

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↗