[The problem of mutagenic side effects of psychotropic substances. 2. Narcotics and addictive drugs].
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Biomedical subjects
Publications and source records attributed to E Gebhart.
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The protective activity of the combined application of anticlastogens against the chromosome-damaging action of Trenimon and bleomycin was studied by analyzing more than 32000 metaphases from cultures of human peripheral lymphocytes. Screening tests with the combinations cysteine/cysteamine/AET, cysteine/methionine/asparagine, cysteine/serine/HCT, and AET/HCT, with Trenimon as clastogen, in no case revealed a hyperadditive (synergistic) effect. From the results of detailed analyses of the action of the combination AET/HCT it was concluded that the (nonsynergistic) anticlastogenic effects observed were induced due to intracellular biologic mechanism, and not due to a reaction in the culture fluid between clastogens and anticlastogens. Although the observations gained with Trenimon or bleomycin differed in some respects, the anticlastogens apparently act via a mechanism at least common to AET and HCT, i.e., they manifest their effect in lymphocyte cultures by a limited interaction with the process of aberration formation, rather than by influencing repair processes, which are blocked by caffeine.
Cytogenetic analyses were carried out in lymphocytes of 37 persons before and during a primary chemoprophylaxis or a preventive chemotherapy with isoniazid as well as of 30 patients suffering from active pulmonary tuberculosis before and during a chemotherapy with isoniazid in combination with two other antimycobacterial drugs. The results of the four participating research groups consistently reveal no indication for a chromosome damaging activity of isoniazid, of its metabolites in the human organism and of the administered drug regimens.
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Comparative studies on human lymphocyte cultures yielded a certain specificity of the anticlastogenic action of the SH compounds l-cysteine, cysteamine, and beta-aminoethylisothiouronium (AET) as well as of the amide l-asparagine and the amino acid l-methionine. This specific anticlastogenic activity manifested itself in specific changes of the spectrum of aberration types induced by the clastogens and of the pattern of intercellular distribution of the induced aberrations. It was clearly dependent on the concentration of the anticlastogens but was also influenced by the used clastogen. The use of different culture media yielded some quantitative influences on the anticlastogenic activity, but fundamental changes in the spectrum of anticlastogenic action have not been observed except with cysteamine. The patterns of activity ascertained for the different anticlastogens specifically differed from those changes in the spectrum and pattern of distribution of aberrations induced by a mere reduction of the concentration for instance of Trenimon. Therefore a direct reaction between the protectors and the clastogen Trenimon as the cause of the observed anticlastogenic action was again excluded. The presented data are also discussed under the aspects of the hypotheses of aberration induction as well as of their importance for further antimutagen research.
The lead content in blood, the excretion of delta-aminolaevulinic acid (ALA) in urine, and the ratio of secondary chromosomal aberrations in lymphocyte cultures were investigated in 105 workers with varying degrees of lead exposure. While the mean lead content was slightly increased (377 plus or minue 207 mug/l) the mean ALA excretion was normal (3,8 plus or minus 4.7 mg/g creatine). Chromosome investigations showed a slightly increased rate of cells with structural abnormalities (14,1 plus or minus 7.0%). Statistical evaluation of these data showed no significant correlation between the lead content in blood, ALA excretion in urine, and cytogenetic findings. No other reason for the increased rate of chromosomal aberrations could be detected.
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Chromosome studies were performed in cultures of peripheral blood lymphocytes drawn from 10 children before and after a therapy with Bactrim (Eusaprim). No significant difference was found between the rate of structural chromosome aberrations, especially the breakage rate, before and after treatment.
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