Search PubMed⌕ Search

Biomedical subjects

E Vogel

Publications and source records attributed to E Vogel.

At least 109 records · Page 6Linked to original sources
PubMed1976

The capacity of Drosophila for detecting relevant genetic damage.

For the detection and study of mutagenic agents, Drosophila offers many advantages. It is a higher organism with a short generation time that is cheap and easy to breed in large numbers. The simple genetic testing methods provide unequivocal answers about the whole spectrum of relevant genetic damage. A comparison of the detection capacity of assays sampling different kinds of genetic damage revealed that various substances are highly effective in inducing mutations, but do not produce chromosome breakage effects at all, or only at much higher concentrations than those required for mutation induction. Of the different assay systems available, the classical sex-linked recessive lethal test thus deserves priority, in view of its superior capacity to detect mutagens. Of practical importance is also its high sensitivity, because a large number of loci in one-fifth of the genome is tested for newly induced forward mutations, including small deletions. Drosophila is capable of carrying out the same metabolic activation reactions as the mammalian liver. An additional advantage, in this respect, is the capacity of Drosophila for detecting short-lived activation products, because intracellular activation occurs within the spermatids ans spermatocytes. These properties make the test for recessive sex-linked lethals a useful tool for verifying results obtained in the pre-screening of potential mutagens with fast microbial assay systems. In studies on non-disjunction, detailed genetic analysis of the induced changes is possible, and these may shed light on the mechanisms involved. A new adaptation of the bithorax transvection method by Mendelson permits the recovery of high yields of chromosome aberrations in a fast one-generation test.

Animals↗
PubMed1976

Assaying potential carcinogens with Drosophila.

Drosophila offers many advantages for the detection of mutagenic activity of carcinogenic agents. It provides the quickest assay system for detecting mutations in animals today. Its generation time is short, and Drosophila is cheap and easy to breed in large numbers. The simple genetic testing methods give unequivocal answers about the whole spectrum of relevant genetic damage. A comparison of the detection capacity of assays sampling different kinds of genetic damage revealed that various substances are highly effective in inducing mutations but do not produce chromosome breakage effects at all, or only at much higher concentrations than those required for mutation induction. Of the different assay systems available, the classical sex-linked recessive lethal test deserves priority, in view of its superior capacity to detect mutagens. Of practical importance is also its high sensitivity, because a large number of loci in one fifth of the genome is tested for newly induced forward mutations, including small deletions. The recent findings that Drosophila is capable of carrying out the same metabolic activation reactions as the mammalian liver makes the organism eminently suitable for verifying results obtained in prescreening with fast microbial assay systems. An additional advantage in this respect is the capacity of Drosophila for detecting short-lived activation products, because intracellular metabolic activation appears to occur within the spermatids and spermatocytes.

Animals↗
PubMed1975

Concentration-effect studies with MMS, TEB, 2, 4, 6-TriCl-PDMT, and DEN on the induction of dominant and recessive lethals, chromosome loss and translocations in Drosophila sterm.

Comparative tests were made with four mutagens, treating male germ cells, particularly mature sperm, of Drosophila melanogaster. Dominant lethals, sex-linked recessive lethals, sex-chromosome loss and partial loss, and in one test translocations were used as genetic and points. The four mutagens, methanesulphonate (MMS), 2,3,5,6-tetraethyleneimino-I,4-benzoquinone (TEB), I(2,4,6-trichlorophenyl)-3,3-dimethyltriazene (2,4,6-triC1-PDMT), and diethyl nitrosamine (DEN) are known to differ in their chemical properties and mode of mutagenic action. An apparent relationship between dominant lethal induction and other genetic damage was found only with TEB. All four mutagens are efficient inducers of sex-linked recessive lethals. At low concentrations there was no direct concentration-frequency relationships. The two direct mutagens, MMS and TEB were effective in the chromosome loss tests. DEN does not induce translocations or any of the other types of damage studied which can be attributed to chromosome breakage. It is concluded that the sex-linked recessive lethal test is a simple and efficient way of preliminary screening chemical mutagens with Drosophila melanogaster.

Animals↗
PubMed1975

Some aspects of the detection of potential mutagenic agents in Drosophila.

The Drosophila system is a valuable test for detecting and characterizing mutagenic agents. Tester strains are available or can be synthesized for determining almost all types of genetical change ranging from gene mutations to chromosome rearrangements in a great variety of cell types of both sexes. Metabolic activation of all groups of indirect mutagens tested so far (aryldialkyltriazenes, cyclophosphamides, nitrosamines, azo-, hydrazo- and azoxyalkanes, aflatoxins, and polycyclic hydrocarbons; about 35 representatives in all), gives strong although indirect support for the considerable metabolizing ability of Drosophila. This capability would be expected from comprehensive biochemical data on bioactivation of foreign compounds in other insects. From a comparison of which types of genetical change are induced at high, low and threshold concentrations, it appears that lethal tests remain the most reliable method for any screening program. Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazenes, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome breakage were the only indicator for mutagenic activity. Moreover, for several mono- and polyfunctional agents, the lowest dose which is still genetically active was definitely lowest for recessive lethals when compared with dominant lethals, chromosome rearrangements or loss. If a new mutagen is discovered by a screening procedure using Drosophila, an accurate picture of its ability to cause either or both gene mutations and chromosome aberrations can be drawn. Such work will be valuable in helping to clarify similar problems in mammalian systems. For instance, it was important to learn that mutagens of the nitrosamine type apparently fail to produce breakage events in Drosophila. Similarly, three cyclophosphamides appeared not to have chromosome breaking ability. However, from a more detailed study, in which a series of concentrations was used, it became obvious that a penetration effect or, more likely, a rate-limiting factor in bioactivation, was the cause of the negative results obtained with these agents.

Animals↗
PubMed1975

Mutagenic activity of cyclophosphamide, trofosfamide, and ifosfamide in drosophila melanogaster. specific induction of recessive lethals in the absence of detectable chromosome breakage.

The mutagenicity of cyclophosphamide (EndoxanR), trofosfamide (IxotenR), and ifosfamide was tested on male germ cells, mainly mature sperm, of Drosophila melanogaster. The genetic end points used were sex-linked recessive lethals, dominant lethals, sex chromosome loss, and partial Y chromosome loss. For recessive sex-linked lethals, all three substances induced a significant increase over the control. The effectiveness was not concentration dependent. None of the compounds induced dominant lethals, or complete or partial loss of the sex chromosome. The results are interpreted to indicate the existence of a rate-limiting factor which acts as restriction on the amount of active metabolite in the target cell. This amount is considered to be lower than that required to cause a detectable increase in chromosome breakage types of damage, but is detectable with the higher resolving power of the recessive lethal test.

Animals↗