Mode of action of antitumour antibiotics: Spectrophotometric studies on the interaction of chromomycin A3 with DNA and chromatin of normal and neoplastic tissue

Nayak, Rabindranath and Sirsi, Madhavarao and Podder, Sunil Kumar (1975) Mode of action of antitumour antibiotics: Spectrophotometric studies on the interaction of chromomycin A3 with DNA and chromatin of normal and neoplastic tissue. In: Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 378 (2). pp. 195-204.

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Abstract

The binding of chromomycin A3, an antitumour antibiotic, to various DNA and chromatin isolated from mouse and rat liver, mouse fibrosarcoma and Yoshida ascites sarcoma cells was studied spectrophotometrically at 29°C in 10−2 M Tris-HCl buffer, pH 8.0, containing small amounts of MgCl2 (4.5 · 10−5−25 · 10−5 M). An isobestic point at 415 nm was observed when chromomycin A3 was gradually titrated with Image and its spectrum shifted towards higher wavelength. The rates and extent of these spectral changes were found to be dependent on the concentration of Mg2+. The change in absorbance at 440 nm was used to calculate apparent binding constant (Ka p M−1) and sites per nucleotide (n) from Scatchard plots for various DNA and chromatins. As expected, values of n for chromatin (0.06–0.10) were found to be lower than that found for corresponding DNA (0.10–0.15). Apparently no such correlation exists between binding constants (Ka p M−1 · 10−4) of DNA (6.4–11.2) and of chromatin (3.1–8.3), but Ka p M−1 of chromatin isolated from mouse fibrosarcoma and Yoshida ascites sarcoma are 1.5–3 times higher than that found for mouse and rat liver chromatin. These differences may be taken to indicate structural difference in nucleoprotein complexes caused by neoplasia. The relevance of this finding to tumour suppressive action of chromomycin A3 is discussed.

Item Type:	Journal Article
Publication:	Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis
Publisher:	Elsevier Science
Additional Information:	Copy right of this article belongs to Elsevier Science.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	09 Jan 2010 07:56
Last Modified:	19 Sep 2010 05:48
URI:	http://eprints.iisc.ac.in/id/eprint/23990

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