RESUMO
DNA unprotected by protamine immediately degraded to fragments of a 200 bp size in the blood flow of experimental animals to be delivered to the innermost compartments of tumor cells. Once absorbed by protamine, DNA fragment remained unchanged in size. For intravenous injection of 1-2 microg, the amount delivered to the cells of intramuscularly grafted tumor RLS was well below several copies on a basis of 1,000 bp. There was no correlation between the amount delivered and DNA-protamine linkage. Protamine protection did not affect DNA's ability to inhibit experimental tumors.
Assuntos
Antineoplásicos/farmacologia , DNA/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Protaminas/metabolismo , Animais , Fragmentação do DNA/efeitos dos fármacos , Masculino , Camundongos , Neoplasias Experimentais/metabolismoRESUMO
Our study showed that protamine (80% w/w to DNA) effectively protected its molecules from degradation by native nucleases of the mammalian blood serum. Exogenous DNA bound to protamine effectively stimulated restoration of cyclophosphamide-induced leukopoiesis in mice. It is suggested that the phenomenon was due to repair processes taking place in hemopoietic stem cells damaged by a cross-linking cytostatic drug such as cyclophosphamide. DNA dosage may be reduced and the original DNA fragment size maintained by DNA binding to protamine. As a result, it might involve longer DNA fragments into repair processes of homologous recombination and eventually increase the cell's chances of getting rid of extensive damage.