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L M Fonshteĭn

Publications and source records attributed to L M Fonshteĭn.

At least 19 recordsLinked to original sources
PubMed1989

[The role of UDP glucuronosyl- and sulfotransferases in the butylhydroxytoluene suppression of the mutagenic action of carcinogenic nitroso compounds and cyclophosphane].

Treatment with butylated hydroxytoluene (BHT) was shown to stimulate the activity of UDP-glucuronosyltransferase and to inhibit that of sulfotransferase in liver of Wistar male rats. Addition of UDP-glucuronic acid to incubation medium in Ames' test using BHT-pretreated subfractions of rat liver resulted in decreased mutagenicity of nitrosodiethylamine, nitrosomorpholine and cyclophosphamide. Further treatment with 3'-phosphoadenosine-5'-phosphosulfate failed to affect mutagenic activity of the promutagens tested. However, an increase in mutagenicity of nitrosomorpholine and cyclophosphamide was observed in application of liver subfractions from intact animals. It was concluded that BHT-induced inhibition of active metabolite production as well as increased production of their glucuronides are responsible for inhibition of mutagenicity of the agents tested. Simultaneous decrease in the yield of sulfates potentiated this effect for nitrosomorpholine and cyclophosphamide.

Animals↗
PubMed1988

[Study of the biotransformation of various antineoplastic agents using the Ames test].

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.

Animals↗
PubMed1987

[Sovol as an inducer of procarcinogen activating microsomal enzymes].

The commercial mixture of polychlorinated biphenyls (Sovol) studied by biochemical and immunochemical methods was found to be an inducer of a wide range of cytochrome P-450 isoenzymes. The induced enzymes activated in the Ames test a series of procarcinogens differing both in structure and in target organs: benz(a)pyrene, 3-methylcholanthrene, nitrosomorpholine, dimethylnitrosamine, aflatoxin B1, orthoaminoazotoluene, 2-acetylaminofluorene, cyclophosphamide and benzidine. According to the parameters the studied Sovol is similar to Aroclor 1254 and may be recommended to be used as an inducer of microsomal enzymes in routine tests for carcinogen screening.

Animals↗
PubMed1987

[The nature of DNA damage and its repair after treatment of bacteria with dioxidine].

The nature of the lethal effect of antimicrobial drug dioxidin was studied. The treatment of bacterial cells by dioxidin results in an instant repression of DNA synthesis and formation of single strand gaps in DNA molecule. The repair of single strand gaps in polA+ cells involves the DNA polymerase I. The deficit of this enzyme leads to the increased degradation of DNA. The products of the recA, polA1, lexA, recB are relevant for bacterial resistance to dioxidin while the products of uvrA, uvrE and recF genes are not. On the basis of the obtained data dioxidin may be defined as a "gamma-type" agent due to the nature of dioxidin-induced lesions in DNA and their repair.

DNA Damage↗
PubMed1987

[Butylhydroxytoluene inhibition of the mutagenic activity of carcinogenic nitroso compounds and cyclophosphamide: the role of the glutathione conjugation reaction].

Mutagenic effect of diethylnitrosamine, nitrosomorpholine and cyclophosphamide were studied on Salmonella typhimurium in the Ames test using S9, microsomal and cytosolic subfractions of Wistar male rats. Pretreatment with butylhydroxytoluene (BHT) was followed by a 50-60% decrease in metabolic activation of the said promutagens by liver subfractions. This was matched by an increase in cytosolic and microsomal glutathione-S-transferase activity and glutathione level in rat liver. The addition of glutathione to the incubation medium in the Ames test using liver subfractions of BHT-treated rats brought on a complete inhibition of mutagenic effect of the agents studied. It is suggested that BHT-induced decrease in production of active metabolites and increase in their inactivation in reactions of glutathione enzymatic conjugation account for the inhibition of mutagenicity of the promutagens under study.

Animals↗
PubMed1987

[Effect of modifiers of the cytochrome P-450-dependent enzyme system of the liver on the metabolic pathways of diethylnitrosamine activation and inactivation].

Pretreatment of Wistar male rats with antioxidants prevented the toxic effect of diethylnitrosamine (DENA) at LD50. Six-fold acceleration of DENA excretion and significant increase of maximum plasma concentration of a DENA metabolite nitrite were, also observed after antioxidants treatment. Liver microsomal metabolism of DNA was altered by pretreatment with another antioxidant--butylhydroxytoluene, which stimulated selectively denitrosation and inhibited dealkylation of DENA in the microsomal cytochrome P-450-dependent enzyme system. Moreover, butylhydroxytoluene treatment diminished he ability of microsomes to activate DENA to mutagenic intermediates identified in Ames' test. It was suggested that the protective effect of antioxidants against DENA toxicity may be due to the acceleration of its metabolic inactivation and the inhibition of its activation in liver cytochrome P-450-dependent systems.

Animals↗
PubMed1987

[Additional pathway of the metabolic activation of N-nitrosodiethylamine in the rat liver].

A cytosolic enzyme, aldehyde oxidase (AO), was shown to be involved in metabolic activation of carcinogenic diethylamine (DENA). DENA was reduced to corresponding hydrazines by AO in the presence of benzaldehyde. Products of DENA reduction by AO possessed mutagenic activity for Salmonella typhimurium TA 1950. Pretreatment of rats by antioxidant butylhydroxytoluene had no effect on this process of DNA bioactivation.

Aldehyde Oxidase↗
PubMed1986

[Study of promutagen biotransformation in the Ames test. III. The role of conjugation with glucuronic acid and sulfate in the modification of mutagenic effect of nitrosomorpholine, diethylnitrosamine and cyclophosphamide].

The role of reactions of conjugation with uridine diphosphoglucuronic acid (UDPGA) and with 3-phosphoadenosine-5-phosphosulfate (PAPS) in modification of the mutagenic effect of diethyl nitrosamine (DENA), nitrosomorpholine (NM) and cyclophosphane (CP) was studied by the Ames test. It was shown that adding UDPGA to the activating mixture significantly decreased the level of the mutagenic effect of DENA, NM and CP on bacteria Salmonella typhimurium TA 1950, when S9 and microsomal fractions of rat liver homogenate were used. Adding PAPS to the activating mixture when S9 and cytosole fractions were used, did not affect mutagenic action of DENA on S. typhimurium TA 1950 and TA 1535, enhancing the mutagenic effect of CP on TA 1535, with no such influence on TA 1950. Introduction of PAPS into the activating mixture elevated the mutagenic effect of NM on both bacterial strains using S9 fraction but not cytosole fraction.

Animals↗
PubMed1986

[Study of promutagen biotransformation in the Ames test. IV. The effect of transplanted tumors on the biotransformation of various antineoplastic agents].

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.

Animals↗
PubMed1985

[Effect of dioxidine, antineoplastic agents and other mutagens on the precise excision of Tn1 and Tn10 transposons in E. coli K12].

Induction of precise excision of transposons Tn1 and Tn10 from the genes met::Tn1 and cys::Tn10 by chemical agents, having mutagenic and DNA damaging activities, has been studied. The drugs dioxydin, NMU, photrin, phopurine, thiophosphamid, rongeron as well as sodium azide, 2-NP, DDDTDP are shown to differ in their ability to stimulate the precise excision of transposons of different classes and in the efficiency of stimulated process. Results of the present paper are in proof of the possible using of experimental model, based on registering the precise excision of transposons, for screening the mutagenic and cancerogenic activities of chemical agents from the environment.

Antineoplastic Agents↗
PubMed1985

[Study of the process of promutagen biotransformation by the Ames test. I. The role of conjugation with glutathione in the modification of the mutagenic activity of nitrosomorpholine, diethylnitrosamine and cyclophosphamide].

It is demonstrated that the level of the action of nitrosomorpholine (NM), diethyl nitrosoamine (DENA) and cyclophosphane (CP) promutagens on bacteria is lowered as a result of the Ames test modification by means of addition of reduced glutathione (G-SH) to the activating mixture. The data are presented on the dependence of this phenomenon on concentration of promutagens and G-SH, the period of bacteria preincubation with the compound under study and the activating mixture as well as on concentration of microsomal protein. No changes in the mutagenic effect of NM, DENA and CP were observed when G-SH was substituted for cysteine in equimolar concentration. This fact points to enzymic mechanism involved in elimination of the damaging effect of mutagenic metabolites of the compounds studied.

Animals↗
PubMed1985

[The process of promutagen biotransformation studied by the Ames test. II. The extent of the manifestation of the mutagenic action of nitrosomorpholine, diethylnitrosamine and cyclophosphane using various subfractions of rat liver homogenate].

The data are presented on involvement of components of microsomal and cytosolic subfractions composing the S-9 fraction of rat liver homogenate in processes leading to formation of active metabolites of nitrosomorpholine (NM), diethyl nitrosoamine (DENA) and cyclophosphane (CP) promutagens and their detoxication resulting from the reaction with glutathione (G-SH) added to the system. It is established that the process of metabolic activation is only connected with microsomal subfraction, while reactions of the first phase of CP and DENA metabolism take place when both microsomal and cytosolic subfractions are added. Decrease in the effect of all promutagens studied under the action of G-SH was observed after microsomal and cytosolic subfractions of the S-9 fraction were introduced into the activating mixture. Various values of dependence of the metabolic activation level and the extent of decrease in the mutagenic action, upon addition of G-SH, on the protein content in microsomal and cytosolic subfractions were obtained.

Animals↗
PubMed1983

[Experimental analysis and planning using the Salmonella/microsomes test].

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.

Microsomes↗
PubMed1982

[Effect of plasmid pKM101 on the mutagenic action of dioxidine in Escherichia coli K-12].

To define the types of base pair substitutions induced by the antibacterial agent dioxydine, the genotypes of Trp+ revertants of the trpA58 and trpA78 missense mutations were studied. Dioxydine was shown to induce transitions and transversions in the plasmidless strains, AT leads to GC transitions and, probably, GC leads to TA transversions exceeding other types of base changes. The strains harbouring pKM101 plasmid had the higher rate of mutations induced by dioxydine due to the increase in frequencies of AT leads to GC transversions and transitions of GC pairs. Thus, the mutator activity mediated by pKM101 results in a significant change in distribution of predominant types of dioxydine-induced base pair substitutions.

Anti-Bacterial Agents↗
PubMed1979

[Mutagenic effect of a tetrahydrodiazopyrene derivative on bacteria].

Mutagenic action of 3,7-diamino-4,9-dioxy-5,10-dioxo-4,5,9,10-tetrahydro-4,9-diazapiren (DDDTDP) was shown using indicator strains Salmonella typhimurium TA 1534, TA 1536, TA 1537, TA 1538. The drug-induced mutations in strains TA 1534 and TA 1538, and it can be used as a positive control in testing mutagens capable of inducing frameshift mutations. No significant differences was observed between DDDTDP effects on strains TA 1534 and TA 1538 which did or did not bear rfa mutation causing defects of cell wall lypopolysacharide complex. Within the range of concentrations tested DDDTDP had mutagenic effect without causing essential killing of bacteria. The mutagenic effect was decreased in the in vitro system of metabolic activation (Ames' plate test in Salmonella microsomes).

Azo Compounds↗
PubMed1978

[Mutagenic activity of dioxydine].

A previous evaluation of mutagenic activity of some drugs and perspective substances is carried out using indicator microorganisms. The mutagenicity of dioxydine, a drag with discovered antibacterial activity, is investigated. Dioxydine is shown to induce reversions in mutant of Salmonella typhimurium TA-1950, the indicator strain which demonstrates mutagenic activity of agents, producing mutations of base pair substitution type. Dioxydine proved to affect logariphmiically growing bacterial culture with great activity. Mutageni effect of dioxydine is not modified itself in microsomal oxidation system in vitro. Some data concerning participation of excision reparation enzyme (uvr-B+ gene product) in repair of lethal damages induced by dioxydine, have been obtained. The dioxydine ability to cause bacterial gene mutations in host mediated assay as well as dominant and recessive sex-linked lethal mutations in Drosophila is demonstrated. Dioxydine is capable of inducing chromosome aberrations in bone marrow cells and dominant lethal mutations in mouse germ cells.

Animals↗
PubMed1976

[Effect of mutagenic metabolic activation of N-nitrosomorpholine on microorganisms].

Almost similar sensitivity is demonstrated of different methods of studying mutagenic metabolic activation of N-nitrosomorpholine (NM) in Salmonella typhimurium TA 1950 (host-mediated assay and the system of metabolic activation with rat liver homogenate). The role of correlation of certain ingredients of NM metabolic activation system with homogenates (homogenate and cofactor NADPH concentrations) is studied. The fact of influence of microsome protein activator (phenobarbital) on the NM mutagen activation effect is established.

Animals↗