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C Ramel

Publications and source records attributed to C Ramel.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibitor of poly(ADP-ribose)transferase potentiates the recombinogenic but not the mutagenic action of alkylating agents in somatic cells in vivo in Drosophila melanogaster.

The effect on somatic mutations and recombination by 3-aminobenzamide (3-ABA), an inhibitor of poly(ADP-ribose) transferase, was studied in the somatic wing spot test in Drosophila melanogaster, 3-ABA did not exert any effect by itself, but caused a strong increase of wing spots in combination with methyl methanesulphonate (MMS) and ethylnitrosourea (ENU). MMS and ENU differ in their mutagenic effects, ENU causing a much higher frequency of point mutations than MMS. The enhancement by 3-ABA of chemically induced wing spots was totally eliminated by the introduction of a heterozygous inversion. It can be concluded that 3-ABA interacted with the chemical mutagens for the induction of somatic recombination, but had no effect on point mutations or intragenic events.

Alkylating Agents↗
PubMed1989

The nature of spontaneous mutations.

The induction of mutations is often expressed in relation to spontaneous mutations and designated for instance by the doubling-dose concept. A problem in that context is the fact that the mutational spectrum for spontaneous and induced mutations is not the same and it can furthermore vary considerably between loci. This is illustrated by molecular characterization of spontaneous and ionizing-radiation-induced mutations in mammalian cells. Furthermore changes of the genetic machinery are not limited to those endpoints usually measured in mutational assays, that is, base substitutions, frameshifts, classical chromosomal aberrations and numerical alterations of chromosomes. Additional alterations, of which far less is known, include insertion mutations, recombinogenic events and disproportionate replication of DNA giving rise to gene amplifications, and changes of gene expression through methylation of cytosine. There are reasons to believe that these endpoints are of importance in the development of tumors. Amplification of oncogenes is a well-known phenomenon in tumorigenicity and lately mutations by the insertion of mobile DNA elements have been demonstrated in cancer cells. Often these alterations are induced by stress and they constitute a manifestation of the dynamics and instability of DNA and the genetic system revealed in recent years. It is of interest in that context that the flow of genetic information does not only occur in one direction that is, DNA-RNA-protein, but also from RNA to DNA through reverse transcription and possibly even from the protein end of the sequence.

Animals↗
PubMed1989

Modifications of the effect of bleomycin in the somatic mutation and recombination test in Drosophila melanogaster.

Exposure to oxygen has been implicated as an important mechanism of mutations, cancer and aging. Most data supporting this notion have been obtained in vitro, but the elaborate defense systems against oxygen stress in aerobic organisms make it difficult to extrapolate in vitro data to in vivo conditions. In the present investigation the somatic mutation and recombination test (SMART) in Drosophila with the wing spot system (Graf et al., 1984) has been used as an in vivo system to study the effect of oxygen radicals generated by bleomycin (BLM). BLM causes a dose-related increase of wing spots and this effect drastically increases by increasing oxygen in the atmosphere to 70%. Data from treatment of larvae of different ages, as well as post-treatment with oxygen, indicate that BLM can persist, presumably intercalated in DNA, and subsequently be activated by oxygen to generate free radicals. By the use of inversion heterozygosity, which eliminates somatic recombination, it was shown that the majority of wing spots induced by BLM emanate from somatic recombination. A small number of flies deviated from the rest by an abnormally high frequency of BLM-induced wing spots. Preliminary results from a selection of such flies indicate that this extreme response to BLM is genetically determined. Treatment with BLM was also combined with agents known to interfere with the defense mechanisms against radicals or function as radical scavengers. Only ascorbic acid cotreatment had a modifying effect on BLM mutagenicity. The other agents did not alter or at most had a marginal effect on BLM mutagenicity. These data indicate that the defense mechanisms do not constitute a limiting factor in this case. BLM intercalates between DNA bases, presumably giving little time and opportunity for modifying agents to react with radicals generated in direct contact with the gene targets. No effect of BLM was observed on male germ cells by measuring loss and non-disjunction of ring-X/Y, neither in air nor in a 70% oxygen atmosphere.

Animals↗
PubMed1988

Mechanisms of inhibitors of mutagenesis and carcinogenesis. Classification and overview.

The mechanisms of action of inhibitors of mutagenesis and carcinogenesis are reviewed in the light of our present knowledge. The identified mechanisms are classified into several categories and sub-categories, depending on the stage of intervention in the mutagenesis and carcinogenesis processes, and on the patterns of modulation of the host defense devices. Although a number of the known mechanisms fit into the proposed scheme, the available information on these problems is still fragmentary, and often inhibitors act through multiple mechanisms or can interact with other inhibitors. Moreover, due to the double-edged nature of many protective factors of the organism, and to the wide array of biological properties displayed by several inhibitors, the beneficial effects are in many instances counter-balanced by adverse reactions. Nevertheless, the present data-base on mechanisms of inhibitors, which is expected to grow rapidly in the near future, provides an extremely useful scientific premise for the primary prevention of mutation-related diseases. In this prospect, the elucidation of the underlying mechanisms complements the results emerging from the monitoring of protective end-points in mutagenicity and carcinogenicity test systems.

Humans↗
PubMed1986

Genetic variation in the susceptibility to mercury and other metal compounds in Drosophila melanogaster.

The tolerance of Drosophila melanogaster to heavy metal compounds was investigated with special emphasis on methylmercury. A pronounced variation in tolerance to CH3HgOH, HgCl2, (C2H5)3PbCl, (CH3)3SnCl, and CdCl2 was recorded between 12 wild-type strains. After ranking the tolerance of the strains with respect to the five compounds rank correlations for experiments within and between compounds were calculated. The results showed a high degree of correlation within compounds but no unequivocal indication of a correlation between compounds, indicating that different mechanisms of genetic control for tolerance were operating for the five compounds. Rank correlations for experiments with 12 different mercury, lead, tin, and cadmium compounds and the same 12 wild-type strains only indicated one significant correlated response, between tripropyltin and tributyltin. A selection experiment for tolerance to methylmercury was performed with a foundation population, synthesized from four wild-type strains, showing a high initial tolerance. One control and two levels of treatment doses were used. A distinct selection response was obtained and a high tolerance was reached particularly for the high-dose selection line after 12 generations, when the experiment ended. Genetic analysis of the tolerance indicated a dominant and polygenic inheritance. Investigation of the uptake and excretion of CH3Hg203OH showed that the level of tolerance to methylmercury was correlated with the uptake of the mercury but apparently not with the rate of excretion. Cystein increased the susceptibility to methylmercury. Inorganic mercury and trimethyl lead exhibited a synergistic toxic effect, evidently as the result of an in vitro transmethylation of mercury. A high somatic susceptibility to methylmercury also applied to the induction of nondisjunction and sex-linked recessive lethals.

Animals↗
PubMed1986

Deployment of short-term assays for the detection of carcinogens; genetic and molecular considerations.

The deployment of short-term assays for the detection of carcinogens inevitably has to be based on the genetic alterations actually involved in carcinogenesis. This paper gives an overview of oncogene activation and other mutagenic events connected with cancer induction. It is emphasized that there are indications of DNA alterations in carcinogenicity, which are not in accordance with "conventional" mutations and mutation frequencies, as measured by short-term assays of point mutations, chromosome aberrations and numerical chromosome changes. This discrepancy between DNA alterations in carcinogenicity and the endpoints of short-term assays in current use include transpositions, insertion mutations, polygene mutations, gene amplifications and DNA methylations. Furthermore, tumourigenicity may imply an induction of a genetic instability, followed by a cascade of genetic alterations. The evaluation of short-term assays for carcinogenesis mostly involves two correlations that is, between mutation and animal cancer data on the one hand and between animal cancer data and human carcinogenicity on the other. It should be stressed that animal bioassays for cancer in general imply tests specifically for the property of chemicals to function as complete carcinogens, which may be a rather poor reflection of the actual situation in human populations. The primary aim of short-term mutagenicity assays is to provide evidence as to whether a compound can be expected to cause mutations in humans, and such evidence has to be considered seriously even against a background of negative cancer data. For the evaluation of data from short-term assays the massive amount of empirical data from different assays should be used and new computer systems in that direction can be expected to provide improved predictions of carcinogenicity.

Carcinogens↗