The mode of action of cytotoxic and antitumor 1-nitroacridines. III. In vivo interstrand cross-linking of DNA of mammalian or bacterial cells by 1-nitroacridines

Chemico-biological Interactions
J KonopaK Pawlak

Abstract

To define a critical lesion in presumable target DNA cause in vivo by the antitumor and cytotoxic 1-nitroacridines, Ehrlich ascites tumor (Eat) cells implanted into mice, HeLa cells grown in monolayer culture or Bacillus subtilis SB 1058 strain cells were exposed to Ledakrin [Nitracrine; 1-nitro-9-(3'-dimethylamino-n-propylamino)acridine], its non-antitumor congeners, or mitomycin C tested for comparison; total intracellular DNA was isolated from control or treated cells and denatured by heat, alkali or formamide, after which the chemically-induced fraction of interstrand cross-linked DNA molecules was assessed by thermal denaturation-renaturation curve analysis, hydroxylapatite column chromatography, or partitioning in a Dextran T500-polyethylene glycol 6000 biphasic system. Ledakrin, as compared to mitomycin C, was a very effective cross-linking agent, inducing one covalent cross-link per approx. 20 X 10(3) (B. subtilis), 56 X 10(3) (HeLa) or 80 X 10(3) (Eat) DNA base pairs. The first cross-links were introduced in B. subtilis cell genomes at minimal bactericidal concentrations of Ledakrin of mitomycin C. Ledakrin failed to induce discernible cross-linking of bihelical DNA when complexed with in cell-free system. Unlike the o...Continue Reading

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Citations

Jun 15, 1994·Biochemical Pharmacology·A Skladanowski, J Konopa
Dec 22, 1995·Chemico-biological Interactions·M ColucciaG Natile
Aug 14, 1989·Biochimica Et Biophysica Acta·L Szmigiero, K Studzian
May 1, 1995·General Pharmacology·M Gniazdowski, L Szmigiero
Jan 1, 1985·Pharmacology & Therapeutics·A M Jeffrey
Jan 25, 2021·Bioorganic & Medicinal Chemistry Letters·Kamila RządIwona Gabriel
Feb 15, 2001·Chemical Research in Toxicology·K GorlewskaJ Konopa

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