RESUMO
The Ames test on indicator bacteria S. typhimurium TA 1950 and TA 100 and the differential spectrophotometry have shown that cytochrome P-450-dependent monooxygenases of mammalian liver participate in the metabolism of antitumour drugs (cyclophosphamide, thiophosphamide) and of nitrosomorpholine (promutagen). Data concerning prospidin indicate that microsomal liver enzymes either induce no metabolic transformations of this preparation or the formed metabolites possess the mutagenic activity similar to that of the parent compound.
Assuntos
Antineoplásicos/farmacocinética , Testes de Mutagenicidade , Mutagênicos/farmacocinética , Animais , Antineoplásicos/toxicidade , Biotransformação , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Mutação , Ratos , Ratos Endogâmicos , Salmonella typhimurium/genéticaRESUMO
The Ames test has shown that the action of nitrosomorpholine and cyclophosphane promutagens on bacteria of Salmonella typhimurium TA 1950 increases while using S-9 liver fraction of rats treated with pharmaceuticals of amidopyrine, reserpine and pyrazidol and decreases while using those treated with phenazepam.
Assuntos
Ansiolíticos , Benzodiazepinas , Mutagênicos/farmacologia , Aminopirina/farmacologia , Animais , Benzodiazepinonas/farmacologia , Carbazóis/farmacologia , Ciclofosfamida/farmacologia , Interações Medicamentosas , Feminino , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Testes de Mutagenicidade , Mutagênicos/metabolismo , Nitrosaminas/farmacologia , Fenobarbital/farmacologia , Ratos , Ratos Endogâmicos , Reserpina/farmacologia , Salmonella typhimurium/efeitos dos fármacosRESUMO
The effect of transplantation of rat tumours Jensen sarcoma, sarcoma 45, sarcoma M-1, as well as of inoculation of rat normal connective tissue on the processes of biotransformation of antitumour preparations cyclophosphane (CP), thiophosphamide, prospidine and of model compound nitrosomorpholine (NM) was studied. The study was accomplished by means of the Ames test with indicator bacterial strain Salmonella typhimurium TA 1950 in relation to the reactions of the 1st and the 2nd phases of xenobiotics metabolism. It was shown that the presence of tumours leads to inhibition of both metabolic activation processes of the promutagens NM and CP and the conjugation reactions of genetically active metabolites of these compounds with reduced glutathione. Genetic danger is supposed to be increased during application of antitumour preparations, the mutagenic activity of which is due to the activity of their metabolites. It is noted that the most essential effect on biotransformation processes of NM and CP was exhibited by sarcoma M-1, the most important changes of the biotransformation processes of promutagens being observed in the initial period of pathologic process, i.e. on the 3rd day after inoculation. Transplantation of the normal connective tissue of rats had no effect on reactions of both the 1st and the 2nd phase of metabolism of the promutagens studied.
Assuntos
Antineoplásicos/toxicidade , Mutagênicos/metabolismo , Sarcoma Experimental/metabolismo , Animais , Antineoplásicos/metabolismo , Biotransformação , Masculino , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade , Transplante de Neoplasias , Ratos , Salmonella typhimurium/genéticaRESUMO
A possible statistical treatment of the results obtained in Salmonella typhimurium TA1950, TA1535, TA1537, TA1538, TA98 and TA100 using the Salmonella/microsomes test was investigated. An analysis of independent repeated experiments pointed to the divergence of the data obtained. Consequently, it has been recommended to carry out the statistical treatment of experimental data within the limits of dispersion analysis with the subsequent use of the Scheffe's method for multiple comparisons. To stabilize the dispersion of experimental data, it is suggested to express the number of revertant colonies as lnX. A minimal volume of the data sample needed for resolving experimental tasks has been calculated. In standard experiments aimed at revealing the mutagenic activity of the compounds used, three Petri dishes should be used in each variant of experiments.
Assuntos
Microssomos/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Projetos de Pesquisa , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Estatística como AssuntoRESUMO
Lethal and mutagenic action of the antibacterial drug dioxidine was studied in bacteria. The mutagenic action of dioxidine is related to rec A-dependent repair process. The effect of the drug was increased due to mutation of rfa in S. typhimurium causing a destruction of the cell wall polyliposaccharide complex. The mutagenic action of dioxidine was studied as applied to isogenic strains of S. typhimurium bearing the pKM-101 plasmid and to strains lacking the plasmid.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Mutagênicos , Quinoxalinas/farmacologia , Alelos , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Plasmídeos/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacosRESUMO
The mutagenic activity was studied for the following 14 psychotropic drugs: aminazinum, fluphenazinum-decanoate, thioproperazinum, reserpinum, chlordiazepoxidum, diazepam, oxazepam, trioxazin, tavor, dipheninum, hexamidinum, benzonalum, carbamazepinum, ethosuximidium. It is shown that carbamazepinum, benzonalum, chlordiazepoxidum considerably increase the frequency of chromosome aberrations in the Allium fistulosum L. cells. These drugs were selected for studying their mutagenic activity on the laboratory animals.
Assuntos
Cromossomos/efeitos dos fármacos , Mutagênicos , Psicotrópicos/toxicidade , Sementes/efeitos dos fármacos , Anticonvulsivantes/toxicidade , Aberrações Cromossômicas , Métodos , Mutagênicos/análise , Tranquilizantes/toxicidadeAssuntos
Anticonvulsivantes/farmacologia , Mutagênicos , Psicotrópicos/farmacologia , Analgésicos Opioides/farmacologia , Animais , Ansiolíticos/farmacologia , Antidepressivos Tricíclicos/farmacologia , Antipsicóticos/farmacologia , Benzodiazepinas , Estimulantes do Sistema Nervoso Central/farmacologia , Aberrações Cromossômicas , Drosophila , Feminino , Antagonistas dos Receptores Histamínicos H1/farmacologia , Humanos , Hipnóticos e Sedativos/farmacologia , Lítio/farmacologia , Linfócitos/ultraestrutura , Dietilamida do Ácido Lisérgico/farmacologia , Masculino , Fenotiazinas , Reserpina/farmacologiaRESUMO
During the final 5.5th to 7th hr of the cycle in presence of BUdR, the human Y-chromosome was delayed in its mitotic condensation in the distal part of the long arm. This part was not homogeneous by the degree of the delay. The unevenly condensed Y-chromosome stained with quinacrine was brightly fluorescent in its stretched part. The fluorescence seemed to correlate with the degree of stretching. The distal part of the long arm was heavily labeled with H3-deoxycytidine thus demonstrating presence of late replicating DNA with GC-base pairs.