The selective response of amphibian embryos to benzimidazole and benzotriazole derivatives

Liedke, Kathe B.; Engelman, Morris; Graff, Samuel

doi:10.1002/jez.1401270202

Cited by 14 publications

(6 citation statements)

References 7 publications

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“…The analogues active as growth inhibitors in Escherichia coli are, in general, the same as those which were found to be inhibitory to developing Rana pipiens embryos by Liedke, Engelman & Graff (1954). An exception is NHB which does not affect the embryos.…”

Section: Discussionmentioning

confidence: 77%

Growth Inhibitors and their Antagonists as Mutagens and Antimutagens in Escherichia coli

Greer

1958

Journal of General Microbiology

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Thirty-five substituted benzimidazoles, benzotriazoles and quinoxalines were tested as growth inhibitors on three mutants of Escherichia coli, strain W, having different purine requirements and on the ciliate Tetrahymena geleii. A number of the compounds, especially those with a nitro group in the benzene ring, were inhibitory. Both organisms were affected in a similar way by the compounds. Several of these analogues were tested for mutagenic activity a t the purine and streptomycin loci in a purine-requiring mutant of E. coli. Only inhibitory compounds were found to be mutagenic ; non-inhibitory concentrations of one analogue, 4-nitrO-6-hydroxybenzimidazole (NHB), were, however, also mutagenic. No specific mutagenesis was demonstrated. NHB was found to increase the rate of mutation as determined by the papilla method. Evidence is presented which eliminates the hypothesis that selection rather than mutagenesis was involved. This analogue did not increase the frequency of mutants in non-dividing cells, and was not incorporated into bacterial DNA. The mechanism of this mutagenesis is thought to include the inhibition of enzymes concerned with DNA synthesis. DNA and RNA and their constituents, purine and pyrimidine precursors and analogues, vitamin B,, and other vitamins, were found to have no effect on the inhibition or mutagenesis produced by NHB. Several amino acid combinations and one non-mutagenic analogue, 4-hydroxy-6-nitrobenzotriazole, were, however, found to interfere with mutagenesis by NHB. These compounds did not affect the frequency of spontaneous mutants. The amino acid combination was effective only when present simultaneously with the mutagen and did not act by a selection mechanism. The mechanism of antimutagenesis by amino acids may involve their ability to increase the growth rate and also to modify the inhibited nucleic acid metabolism. The mutagenesis by 5-nitroquinoxaline, a pterin analogue, was also found to be depressed by amino acids in the same purine-requiring mutant. The annulment of mutagenic activity by amino acids was strain and mutagen specific. Twenty-five known inhibitors of nucleic acid synthesis and antagonists to inhibition were tested for mutagenic activity in five strains of Eschmichia coZi. Several, including 6-mercaptopurine, were found to be mutagenic ; in addition, NHB, 5-nitroquinoxaline and 5-aminouracil were mutagenic in most of the strains tested. The mutagenic activity of 5-aminouracil was not annulled by thymine, thymidine or other nucleic acid components, but the mutagenesis of 6-mercaptopurine was annulled by purine bases and by ribosides.

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Section: Discussionmentioning

confidence: 77%

Growth Inhibitors and their Antagonists as Mutagens and Antimutagens in Escherichia coli

Greer

1958

Journal of General Microbiology

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“…(except where solubility was limited) in the experiments on young embryos, and at a considerably lower concentration in the experiments on tadpoles (see below). Six of these compounds had been used in earlier experiments (Liedke, Engelman, & Graff, 1954, 19576) and were used again to broaden the base of comparison. 2-cell, blastula, neurula, and tail-bud stages…”

Section: Resultsmentioning

confidence: 99%

“…The methods were the same as those described in an earlier communication (Liedke, Engelman, & Graff, 1955). For a given experimental series, embryos from the same egg-batch were used.…”

Section: Methodsmentioning

confidence: 99%

“…SUBSTITUTED benzotriazoles (Bt) have been shown to bring about interesting inhibitory effects on Rana pipiens embryos of 2-cell to tail-bud stages (Liedke, Engelman, & Graff, 1954. These benzotriazoles did not have selective cytotoxic effects on sensitive embryonic structures as similarly substituted benzimidazoles (Bz) and quinoxalines (Q) invariably did.…”

Section: Introductionmentioning

confidence: 99%

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Embryonic Responses to Structurally Related Inhibitors

1960

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Substituted benzotriazoles (Bt) have been shown to bring about interesting inhibitory effects on Rana pipiens embryos of 2-cell to tail-bud stages (Liedke, Engelman, & Graff, 1954, 1955, 1957a, 1957b). These benzotriazoles did not have selective cytotoxic effects on sensitive embryonic structures as similarly substituted benzimidazoles (Bz) and quinoxalines (Q) invariably did. The latter compounds, Bz and Q, were most active against younger stages, especially those in cleavage. On the other hand, it was found that the susceptibility to the benzotriazoles increased with age of embryo; more differentiated stages were affected most. The type of response was determined by the parent structure, but certain substituents, the nitro group in particular, appeared to enhance the magnitude of the effect. The activating effect of the nitro group was in turn modified to varying degree by an accompanying methoxy, hydroxy, or amino group.

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“…This expectation has been fulfilled, as was first shown by Brachet (1944) in the cases of barbituric acid, benzimidazole and acriflavine. These early studies have been considerably extended by Bieber (1954), Bieber and Hitchings (1955) and Liedke et al (1954Liedke et al ( , 1957a, who used a considerable number (more than one hundred) of chemical analogues of purines, pyrimidines and nucleosides. They usually found inhibition of development at a definite stage.…”

Section: Considerable Experimental Work Would Be Required In Ordermentioning

confidence: 99%

The biological role of ribonucleic acids

Brachet¹

1960

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Next to nothing was known a quarter of a century ago about the biological role and the intracellular localization of the nucleic acids. All that was well established was the existence of two different types of nucleic acids, which correspond to the deoxyribonucleic (DNA) and ribonucleic (RNA) acids of the present day. They were called, respectively, thymonucleic and zymonucleic acids, because purified preparations had only been obtained from thymus and yeast. It was erroneously believed that thymonucleic acid (DNA) is specific to animal cells and that yeast nucleic acid (RNA) is present only in plant cells. However RNA had been isolated from pancreas. A popular hypothesis was that DNA, which was known to contain both ortho-phosphoric acid and nitrogenous bases, might play the role of an intra-nuclear buffer. Such a role is certainly a minor one for the bearer of "genetic information"! One of the first important advances made in the field came from cytochemistry, when in 1924 Feulgen and Rossenbeck designed and utilized their well-known reaction for the detection of DNA. They were immediately able to demonstrate that thymonucleic acid (DNA) is specifically located in the cell nucleus, in plants as well as in animals. Progress on the role and localization of RNA was slower to come, because of the lack of specific cytochemical reactions comparable to the Feulgen tests. Indirect observations by Brachet (1933) strongly suggested, however, that animal cells may contain such References p. 50/54 RIBONUCLEIC ACIDS AND PROTEIN SYNTHESIS in RNA. Values up to 11.5% dry weight have been reported by Vendrely (1946). Work carried out in several different laboratories shows the existence of an excellent correlation between the synthesis of RNA and the synthesis of proteins, provided that the bacterial growth is studied during the logarithmic phase. For instance, Caldwell et al. (1950) found the RNA content of bacteria to be proportional to the growth rate, whatever the experimental conditions (changes in the nitrogen source of the culture medium, presence or absence of inhibitors, normal organisms or slow-growing mutants). Similar findings have been reported by Northrop (1953), Wade (1952) and Price (1952). An important study of Gale and Folkes (1953) shows that staphylococci synthesize proteins in the presence of glucose and amino acids. If purines and pyrimidines are added to this medium, nucleic acids are also synthesized. But the interesting fact is that if the medium contains no amino acids there is no nucleic acid synthesis, whereas the presence of purines and pyrimidines in the medium enhances protein synthesis. There thus exists a strong positive correlation between the nucleic acid content of the cells and the rate of protein synthesis. Gale and Folkes (1953) have also found that protein synthesis and RNA synthesis can be dissociated by the use of antibiotics. For instance, Chloromycetin, aureomycin, and terramycin all inhibit protein synthesis but increase nucleic acid synthesis. However, there is very good evidence (N...

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The selective response of amphibian embryos to benzimidazole and benzotriazole derivatives

Cited by 14 publications

References 7 publications

Growth Inhibitors and their Antagonists as Mutagens and Antimutagens in Escherichia coli

Growth Inhibitors and their Antagonists as Mutagens and Antimutagens in Escherichia coli

Embryonic Responses to Structurally Related Inhibitors

The biological role of ribonucleic acids

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