Thermodynamics of the cleavage of DNA induced by adriamycin: a microcalorimetric study

Microcalorimetry was used to measure the change in enthalpy for the scissio n of calf thymus DNA (ct-DNA) induced by adriamycin (ADM) in the presence o f ferric ions, Vitamin C, and oxygen. At 298.15 K and pH 7.4, the overall m olar reaction enthalpy for this cleavage was -147.1 kJ/mol, noticeably high er than that by the mixture of Fe3+, Vitamin C, and O-2 Under the same cond itions, the enthalpy change for the damage of ct-DNA by the mixture of adri amycin, ferrous ions, and oxygen, however, was nearly zero, indicating that this mixture can not induce any detectable degradation of DNA. These resul ts suggest that both the activated adriamycin and hydroxyl radical attack D NA strands during the cleavage. A possible mechanism for the cleavage of DN A induced by adriamycin is proposed based on the calorimetric measurements. A novel thermodynamic model for the interactions of DNA with small molecul es is also suggested. This is a convenient method to calculate both the bin ding constant (K-b) and the standard thermodynamic parameters (Delta(b)H(m) (0), Delta(b)C(m)(0), and Delta(b)S(m)(0)) for the binding of adriamycin-Fe 3+ complex to ct-DNA by the calorimetric data. This nucleotide binding reac tion is driven by a favorable enthalpy change, with a large unfavorable ent ropy change. This result indicates that the binding results in structural c hanges accompanied by an increase in the order of the whole system, implyin g that an intercalation mode is involved in adriamycin-mediated breakage of DNA. (C) 2000 Elsevier Science B.V. All rights reserved.