Disease relevance of Nigrin

• The extreme toxicity of streptonigrin is also seen in the response of DNA synthesis which is inhibited sharply in both A-T and normal cells using doses of up to 125 ng/ml, although the effect was less pronounced in A-T cells [1].
• The antitumor compounds were reduced in the following order by rat E. coli DTD: 2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone > streptonigrin > mitomycin A > diaziquone > mitomycin C (MC) > 5-(aziridin-1-yl)-2,4-dinitrobenzamide [2].
• Effects of the DNA strand-cleaving antitumor agent, streptonigrin, on ataxia telangiectasia cells [1].
• Several antitumor drugs are shown to be mutagenic in murine thymoma lines: mitomycin C, bleomycin, streptonigrin, Colcemid, and BD40, an analog of ellipticine [3].
• The generation of oxygen reduction products by Neisseria gonorrhoeae FA1090 upon exposure to streptonigrin (SNG) and paraquat (PQ2+) and their toxicity was examined [4].

High impact information on Nigrin

• Complementation group D A-T fibroblasts were transfected with an episomal vector-based human cDNA library, approximately 610,000 resultant transformants were treated with the radiomimetic drug streptonigrin-resistant, and nine unrelated cDNAs were recovered from 29 surviving streptonigrin-resistant clones [5].
• Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin [6].
• A linear dose-dependent cell survival was observed for both normal and A-T cells exposed to streptonigrin (up to 1.5 ng/ml) for 3-hr, with the A-T cells being about twice as sensitive as were the normal cells (Do approximately 0.25 ng compared with Do approximately 0.5 ng) [1].
• ES936 abrogates the toxicity of streptonigrin, with greater effects seen in cell lines expressing higher levels of NQO1 [7].
• The interaction of volkensin with HeLa cells was compared to that of nigrin b, as an example of a type 2 RIP with low toxicity, and of ricin, as a reference toxin [8].

Chemical compound and disease context of Nigrin

• A tryptophan C-methyltransferase involved in streptonigrin biosynthesis in Streptomyces flocculus [9].
• Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae [10].
• P. aeruginosa showed less cyanide-insensitive respiration than E. coli upon exposure to other redox-active compounds (paraquat, streptonigrin, and plumbagin) [11].
• Purification and characterization of S-adenosylhomocysteine deaminase from streptonigrin-producing Streptomyces flocculus [12].
• The effects of streptonigrin were reversed in pancreatic cancer cells pretreated with dicumarol, a known inhibitor of NQO1 [13].

Biological context of Nigrin

• Finally, chromosomes from both A-T lymphocytes and fibroblasts show about a doubling of breakage rate following exposure to streptonigrin [1].
• Nigrin b and volkensin bound to cells with comparable affinity (approx. 10(-10) M) and had a similar number of binding sites (2 x 10(5)/cell), two-log lower than that reported for ricin [8].
• An S. pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S. pneumoniae systemic infection [14].
• We show that both NM3 and UV40 are also hypersensitive to other DNA crosslinking agents (including diepoxybutane and chlorambucil) and to non-crosslinking DNA damaging agents (including bleomycin, streptonigrin and EMS), and that all these sensitivities are all corrected upon transfection of the human FANCG/XRCC9 cDNA [15].
• Ataxia telangiectasia (A-T) cells are unusually sensitive to streptonigrin, but we show here that they can perform excision repair, as demonstrated by UDS, at the same level as normal cells following exposure to the drug [16].

Anatomical context of Nigrin

• Streptonigrin is an antitumour antibiotic, which at low doses produces DNA strand breaks in cultured cells leading, e.g., to decreased colony-forming ability and decreased rates of DNA synthesis [16].
• Nigrin b was found to be an rRNA N-glycosidase of the rRNA of intact mammalian ribosomes and shares a very good N-terminal amino-acid sequence homology with the anti-HIV-1 proteins TAP 29 and trichosanthin [17].
• The effect of washing lymphocytes after in vivo treatment with streptonigrin on the yield of chromosome and chromatid aberrations in blood cultures [18].
• CHO cells were pulse-treated for 20 min with increasing doses of streptonigrin (SN) [19].
• Evaluation of chemically induced cytogenetic lesions in rabbit oocytes. III. A postimplantation analysis of streptonigrin effects [20].

Associations of Nigrin with other chemical compounds

• Addition of the precursors shikimate and dihydroxybenzoate to strain AB2847 (aroB) and dihydroxybenzoate to strain AN193 (entA), allowing these strains to make enterochelin, resulted in an increase in Fe3+ uptake and a corresponding sharp increase in killing by streptonigrin [21].
• We treated CHO cells with streptonigrin (SN) alone, in combination with BrdUrd or IdUrd substitution, and with or without the addition of caffeine [22].
• Enhancement of chromosome aberrations by the combination of DNA substitution with halogenated deoxyuridine and streptonigrin treatments [22].
• Photogeneration of superoxide and decarboxylated peptide radicals by carboquone, mitomycin C and streptonigrin. An electron spin resonance and spin trapping study [23].
• We compared the frequency of chromosome-type aberrations in human lymphocytes following treatment with two powerful clastogens, streptonigrin and Trenimon, using conventional staining techniques and chromosome painting [24].

Gene context of Nigrin

• Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage-independent growth in soft agar [13].
• Cells deleted for Brca2 exon 27 are hypersensitive to gamma-radiation, streptonigrin, mitomycin C and camptothecin and mildly resistant to ICRF-193 which is similar to HR defective cells null for Rad54 [25].
• Isolation by streptonigrin enrichment and characterization of a transferrin-specific iron uptake mutant of Neisseria meningitidis [26].
• The feoB mutant was also 2.5 logs more resistant to streptonigrin than wild-type 130b, confirming its decreased ability to acquire iron during extracellular growth [27].
• Mutation of either sirA or sirB increased the resistance of iron-starved S. aureus to streptonigrin and resulted in compromised growth in iron-restricted, but not iron-rich, media [28].

Analytical, diagnostic and therapeutic context of Nigrin

• Compounds such as mitomycin C and streptonigrin are efficiently bioactivated by NQO1 and have been used in an enzyme-directed approach to chemotherapy [29].
• Using absorption, circular dichroism, and fluorescence measurements, we have shown that streptonigrin forms with Au(III) a 1:1 Au(III)-streptonigrin complex [30].
• Anti-PiaA and anti-PiuA polyclonal rabbit antibodies bound to the surface of live S. pneumoniae when assessed by flow cytometry but did not inhibit growth of S. pneumoniae in cation-depleted medium or bacterial susceptibility to the iron-dependent antibiotic streptonigrin [31].
• Confocal microscopy showed the rapid localization of volkensin in the Golgi stacks with a perinuclear localization similar to that of ricin, while nigrin b was distributed between cytoplasmic dots and the Golgi compartment [8].
• To investigate the chemosensitivity of A-T heterozygote cell lines, we used TUNEL to analyse the level of apoptosis after drug treatment with etoposide and streptonigrin [32].

References