Increased Deoxyribonucleic Acid Polymerase and Adenosine Triphosphate-Dependent Deoxyribonuclease Activity in Mycobacterium smegmatis after Treatment with Alkylating Agents

1974 ◽  
Vol 2 (4) ◽  
pp. 724-726 ◽  
Author(s):  
ALASDAIR W. MACNAUGHTON ◽  
FRANK G. WINDER
Keyword(s):  
Adenosine Triphosphate ◽  
Mycobacterium Smegmatis ◽  
Deoxyribonucleic Acid ◽  
Alkylating Agents ◽  
Deoxyribonuclease Activity

The influence of radiomimetic substances on deoxyribonucleic acid synthesis and function studied in Escherichia coli / phage systems V. A comparison of the inactivation of phages T 2, T 7 and two strains of T 4 by alkylating agents

1959 ◽  
Vol 151 (942) ◽  
pp. 148-155 ◽  
Keyword(s):  
Deoxyribonucleic Acid ◽  
Osmotic Shock ◽  
Alkylating Agents ◽  
Acid Synthesis ◽  
Acid Moiety ◽  
Rate Of Penetration ◽  
Injection Process ◽  
Deoxyribonucleic Acid Synthesis ◽  
And Function ◽  
Escherichia Coli Phage

The sensitivity of phage T 7 to epoxides and freshly prepared solutions of di(2-chloroethyl) methylamine ( HN 2) was identical with that of T 2. T 7, however, proved considerably the more sensitive to ethylenimine and to aged solutions of HN 2. It was considered that this was due to the cationic nature of these latter agents affecting the rate of penetration into the phage heads, and that the susceptibility of T 2 and resistance of T 7 to osmotic shock was a parallel phenomenon. Confirmation was afforded by the fact that a strain of T 4 sensitive to osmotic shock behaved like T 2, and a resistant strain of T 4 like T 7. These results, together with others previously reported, are believed to offer very strong evidence that inactivation of bacteriophage by alkylating agents derives from reaction with the deoxyribonucleic acid moiety, probably leading to a failure of the injection process.

Die Beeinflussung des Wachstums des Ehrlich-Ascites-Tumors der Maus durch native und mit ultraviolettem Licht bestrahlte heterologe Desoxyribonucleinsäure

1963 ◽  
Vol 18 (7) ◽  
pp. 523-525 ◽  
Author(s):  
Rudolf K. Zahn ◽  
Ekkehard Tiesler
Keyword(s):  
Tumor Growth ◽  
Uv Irradiation ◽  
Deoxyribonucleic Acid ◽  
Tumor Development ◽  
Ehrlich Ascites Tumor ◽  
Ascites Tumor ◽  
Ehrlich Ascites ◽  
Ascites Tumors ◽  
Deoxyribonuclease Activity

1. Deoxyribonuclease activity has been determined by viscosimetry in the serum of the Ehrlich Ascites in the mouse to be equivalent to 2,3 ± 0,7·10-6 g/ml of crystalline beef pancreas DNase.2. Injections of heterologous deoxyribonucleic acid into the Ehrlich Ascites tumor under specified conditions does not alter tumor development.3. The same DNA however becomes strongly inhibitory for tumor growth after UV irradiation.4. Possible implications are discussed.

scholarly journals Mycothiol-Deficient Mycobacterium smegmatis Mutants Are Hypersensitive to Alkylating Agents, Free Radicals, and Antibiotics

2002 ◽  
Vol 46 (11) ◽  
pp. 3348-3355 ◽  
Author(s):  
Mamta Rawat ◽  
Gerald L. Newton ◽  
Mary Ko ◽  
Gladys J. Martinez ◽  
Robert C. Fahey ◽  
...  
Keyword(s):  
Free Radicals ◽  
Mycobacterium Smegmatis ◽  
Parent Strain ◽  
Alkylating Agents ◽  
Single Amino Acid ◽  
Chemical Mutagenesis ◽  
Penicillin G ◽  
Phenotypic Analysis ◽  
Wide Range ◽  
Transposon Mutants

ABSTRACT Mycothiol (MSH; 1d-myo-inosityl 2-[N-acetyl-l-cysteinyl]amido-2-deoxy-α-d-glucopyranoside) is the major low-molecular-weight thiol produced by mycobacteria. Mutants of Mycobacterium smegmatis mc2155 deficient in MSH production were produced by chemical mutagenesis as well as by transposon mutagenesis. One chemical mutant (mutant I64) and two transposon mutants (mutants Tn1 and Tn2) stably deficient in MSH production were isolated by screening for reduced levels of MSH content. The MSH contents of transposon mutants Tn1 and Tn2 were found to be less than 0.1% that of the parent strain, and the MSH content of I64 was found to be 1 to 5% that of the parent strain. All three strains accumulated 1d-myo-inosityl 2-deoxy-α-d-glucopyranoside to levels 20- to 25-fold the level found in the parent strain. The cysteine:1d-myo-inosityl 2-amino-2-deoxy-α-d-glucopyranoside ligase (MshC) activities of the three mutant strains were ≤2% that of the parent strain. Phenotypic analysis revealed that these MSH-deficient mutants possess increased susceptibilities to free radicals and alkylating agents and to a wide range of antibiotics including erythromycin, azithromycin, vancomycin, penicillin G, rifamycin, and rifampin. Conversely, the mutants possess at least 200-fold higher levels of resistance to isoniazid than the wild type. We mapped the mutation in the chemical mutant by sequencing the mshC gene and showed that a single amino acid substitution (L205P) is responsible for reduced MSH production and its associated phenotype. Our results demonstrate that there is a direct correlation between MSH depletion and enhanced sensitivity to toxins and antibiotics.

scholarly journals Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3′-5′)thymidine

1978 ◽  
Vol 171 (3) ◽  
pp. 575-587 ◽  
Author(s):  
D H Swenson ◽  
P D Lawley
Keyword(s):  
Alkyl Group ◽  
Deoxyribonucleic Acid ◽  
Dimethyl Sulphate ◽  
Alkylating Agents ◽  
Electrophilic Reagent ◽  
Relative Reactivity ◽  
Ethyl Methanesulphonate ◽  
A Value ◽  
Phosphodiester Group ◽  
Steric Accessibility

1. The ethyl phosphotriester of thymidylyl(3′-5′)thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates.

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