Many anticancer drugs exert their biological activity by formation of DNA interstrand crosslinks (ICLs),nevertheless the thermodynamics of biologically relevant long crosslinked DNAs is poorly studied in contrast to short duplexes.However,the mechanism underling the ICL thermal effect is different for them: prohibition of full strand separation for duplexes and formation of additional loops for long DNAs.Here,we carry out computer modeling of the shift of melting temperature caused by ICLs taking into account crosslinking effect in itself and concomitant local alterations in the free energy (δG) of the helix-coil transition at sites of ICLs.Depending on δG,DNA interstrand crosslinks at per nucleotide concentration 0.05 can change the melting temperature by value from -17oC to +47oC,and the influence weakly depends on DNA sequence and GC content.The pure crosslinking effect also depends on δG,but it is always positive (0-12oC).Comparison with experiment for the three platinum crosslinking compounds demonstrated rationality of the applied theoretical method.On the basis of the method,the effect on thermal stability caused by interdependence of local distortions and formation of additional loops was studied.A method for evaluation of structural constituent of the change in thermal stability for short crosslinked DNA is also proposed.The methods can be used for comparative thermodynamic characterization of various DNA crosslinking agents.