Hyperthermy Increase the Phosphorylation of Deoxycytidine in the Membrane Phospholipid Precursors and Decrease its Incorporation into DNA

Conclusions

Concerning our results, dCK seems to be the most important deoxynucleoside kinase in resting phase cells, or in cells with DNA damages to be repaired. The DNA damage might be induced by different nucleoside analogues, inhibitors of DNA synthesis. Deoxyadenosine and its analogues, their triphosphates are inhibitors of the DNA repair itself, might be pushing the corresponding salvage kinase in a “more” active form, probably by the secondary modification of the enzyme, to produce deoxynucleotides for repairing DNA.

The local and hole body hyperthermia in cancer therapy might be an additional therapy, to stop DNA replication in cells, which seems to be more sensitive, than nucleoside kinases. At elevated temperatures cells will be filled up with activated deoxynucleosides to be able to repair their DNA. During the mean time cells might be accumulate also phosphorylated nucleoside analogues ready to inhibit DNA synthesis. The activity of dCK was slightly but dTK was even better decreased by the temperature stress of the cells (data not shown).

Thus, the increase in the labelling of membrane phospholipid precursors, seems to be a consequence, that higher temperature stops the flow of dCTP into DNA, but not into membranes The uptake and phosphorylation of deoxynucleosides (i.e. also analogues) seem to be enhanced by mild hyperthermy, while under same conditions, the interconversion(s) between dCyt-dThd and/or the DNA replication machinery are irreversible destroyed.