[Leukocyte stimulation by DNA fragments shored up protamine in cyclophosphamide-induced leukopoiesis in mice].

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.

[Protamine association with exogenous DNA's versus its ability to inhibit experimental tumors].

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.

[Effect of exogenous dna injection on leukopoietic repair and antitumor action of cyclophosphamide].

The cytostatic drug cyclophosphamide (CPA) in high dosage suppressed hemopoiesis by causing multiple double-strand breaks to occur in hemopoietic cell DNA and leading to mutation, chromosomal abberations and finally cell death. We tested fragmented DNA drugs for an ability of CPA to protect murine leukopoiesis on an assumption that once exogenous fragmented DNA had infiltrated into a cell, it might integrate with chromosomal DNA through homologous recombinations thus repairing damaged segments. DNA drugs did promote repair of leukocyte count in murine peripheral blood with leukopoiesis being suppressed by CPA administration. The levels of DNA derived from murine organs and human placenta were higher than those from salmon roe. Tumor growth was significantly inhibited following injection of placental DNA into mice bearing intramuscularly transplanted lymphosarcoma. Antitumor effect of combined CPA and DNA treatment was much higher than after CPA alone.

[Effect of exogenous DNA on the growth of transplantable tumors].

Using transplantable Ehrlich ascites tumor, hepatoma HA-1 and Lewis carcinoma it was shown, that preparations of fragmented genomic DNA can more or less effectively inhibit such tumors as well as the growth of their metastases. Such effects were produced by DNA preparations derived from tissues of mice, both syngeneic or allogeneic to tumor-bearer, as well as from human tissues.

[Specific DNA sequences are associated with nuclear envelopes of pseudonurse cells in Drosophila melanogaster otu 11].

Nuclei of ovarian pseudonurse cells from the mutant strain of Drosophila melanogaster otu 11 are suitable for mapping the attachment of chromosomes to the nuclear envelope (NE). Loci in contact with the NE included region 20CD of the X chromosome, region 41 of chromosome 2, the proximal end of region 81 of chromosome 3, and region 101 of chromosome 4. In situ hybridization revealed that all 4 regions contained sequences homologous to clone lambda20p1.4. DNA of clone lambda20p1.4 was previously found to bind specifically to purified D. melanogaster lamins. These results suggest that specific DNA sequences are involved in attachment of chromosomes to NE in vivo.

[A combined approach to mapping the proximal border of the right arm of polytene chromosome 2 in Drosophila melanogaster otu 11].

A combined approach based on cytological observations in situ hybridization, and qualitative Southern-blot analyses were used to localize the proximal border of the right arm of polytene chromosome 2 in Drosophila melanogaster otu 11 strain. A genetically functional chromosome 2 is bounded by "deletions" C', C, D, B, A and ms2-10. Using in situ hybridization in conjunction with comparative quantitative Southern-blot hybridization to deletions in centromeric heterochromatin, DNA of specific centromeric clone lambda20p1.4 was localized with respect to "deletions" and on otu 11 polytene chromosomes. Comparison of hybridization sites of lambda20p1.4 on polytene chromosomes, and its amount in mutant lines of D. melanogaster carrying known "deletions" in the centromeric heterochromatin enabled us to localize the proximal border of the right arm of chromosome 2 in D. melanogaster otu 11 strain between the 39/40 region and hybridization site of the k20p1.4 DNA fragment.