MICROCALORIMETRIC INVESTIGATION OF MITOXANTRON INFLUENCE ON CHROMATIN DNA IN-VIVO

The influence of antitumor preparation - mitoxantron 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 denaturated in two stages. The first stage - thermolable domain is characterized by the transition parameters: T(d)1 = 72, DELTAT(d)1 = 6.2-degrees-C, Q(d) = 36.5 J/g DNA, the second stage - thermostable domain: T(d)2 = 83, DELTAT(d)2 = 9.0-degrees-C, Q(d) = 58 J/g DNA. The intraperitoneal injection of mitoxantron 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 denaturates in three stages with the following transition parameters: the first, the most thermolable domain with T(d)0 = 56.0, DELTAT(d)0 = 5.0-degrees-C, Q(d) = 20 J/g DNA; the second - thermolable domain with T(d)1 = 72.0, DELTAT(d)1 = 6.2-degrees-C, Q(d)1 = 16.5 J/g DNA; the third - thermostable domain with T(d)2 = 83.0, DELTAT(d)2 = 9.0-degrees-C, Q(d)2 = 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 mitoxantron to leukemic mice causes such changes in chromatin denaturation parameters that curve profile becomes similar to that of normal spleen tissue. We conclude that mitoxantron causes transformation of spleen tumor cells into normal ones in vivo.