The mode of action of cytotoxic and antitumor 1-nitroacridines. II. In vivo enzyme-mediated covalent binding of a 1-nitroacridine derivative, Ledakrin or Nitracrine, with dna and other macromolecules of mammalian or bacterial cells

Chemico-biological Interactions
J W PawlakJ Konopa

Abstract

Earlier evidence, in Part I of this paper, has shown that cytotoxic and antitumor 1-nitroacridines did not primarily exert their potent inhibitory effects on cultured mammalian cells by physicochemical binding with DNA, although it undoubtedly occurred (Chem.-Biol. Interact., 43 (1983) 131). As a result it was investigated (i) whether 9-14C- or 1'-14C-labeled derivatives of their representative, 1-nitro-9-/3'-dimethylamino-n-propylamino/acridine (Ledakrin or Nitracrine), were capable of covalent binding with nucleic acids and other suitable macromolecules in target cells in vivo and/or (ii) whether activation of the agent in the cell was a necessary prerequisite for such binding. Using the criteria of resistance to exhaustive extractions with trichloroacetic acid and/or organic solvents, [14C]Ledakrin was found to bind covalently, with relatively little discrimination, with: (i) intracellular macromolecules, including DNA, of cultured tumor HeLa cells (370-2500 DNA base pairs/one Ledakrin molecule; (ii) experimental animal tumor Ehrlich ascites (Eat) cells in vivo (650-5880 DNA base pairs/one Ledakrin molecule); (iii) bacterial Bacillus subtilis SB 1058 cells (7000-33 000 Ledakrin links/one cell genome); (iv) NADPH-fortified ra...Continue Reading

References

Sep 6, 1977·Biochimica Et Biophysica Acta·J FilipskiM Chorazy

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Citations

Aug 14, 1989·Biochimica Et Biophysica Acta·L Szmigiero, K Studzian
Feb 28, 1997·Chemico-biological Interactions·A BartoszekJ Konopa
Jul 28, 1999·Biochemical Pharmacology·M C HerzigJ M Woynarowski
May 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I G RobertsonB D Palmer
Jan 1, 1985·Pharmacology & Therapeutics·A M Jeffrey
Sep 1, 1991·Mutation Research·L R Ferguson, W A Denny
Feb 15, 2001·Chemical Research in Toxicology·K GorlewskaJ Konopa

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