[Microcalorimetric study of the effect of mitoxantrone on chromatin DNA in vivo]

The influence of antitumor preparation--mitoxantrone on chromatin in tumor cell composition of BALB/c mouse spleen tissue was studied by the method of scanning microcalorimetry. It was shown that chromatin in normal cell composition denatured in two stages. The first stage--thermolabile domain is characterized by the transition parameters: T1d = 72, delta T1d = 6.2 degrees C, Qd = 36.5 J/g DNA, the second stage--thermostable domain: T2d = 83, delta T2d = 9.0 degrees C, Qd = 58 J/g DNA. The intraperitoneal injection of mitoxantrone to healthy mice slightly changes the structural parameters of chromatin but promotes the significant redistribution of heat between peaks, i.e. the part of heterochromatin fraction passes to euchromatin. In the case of leukemia, chromatin denatures in three stages with the following transition parameters: the first, the most thermolabile domain with T0d = 56.0, delta T0d = 5.0 degrees C, Qd = 20 J/g DNA; the second--thermolabile domain with T1d = 72.0, delta T1d = 6.2 degrees C, Q1d = 16.5 J/g DNA; the third--thermostable domain with T2d = 83.0, delta T2d = 9.0 degrees C, Q2d = 58.0 J/g DNA. It is affirmed that the first stage is connected with melting of "naked" DNA regions in tumor chromatin composition. The injection of mitoxantrone to leukemic mice causes such changes in chromatin denaturation parameters that curve profile becomes similar to that of normal spleen tissue. We conclude that mitoxantrone causes transformation of spleen tumor cells into normal ones in vivo.