Dalayed Effects of Antitumor Drug Paclitaxel on the Hereditary Material and Hemopoietic System of CBA Mice.

Paclitaxel in a single MTD of 40 mg/kg caused chromosome aberrations and genome changes (polyploidy) in the bone marrow cells of mice early and 3 months after the injection. The quantity of early precursors of erythropoiesis in the bone marrow decreased, as did their proliferative potential irrespective of the animal gender. Injection of paclitaxel in the MTD caused the development of bone marrow hypoplasia during the early period of observation (up to 14 days) and 3 months after injection.

[Effect of Scutellaria baicalensis root extract on cytogenetic damage induced by paclitaxel and cisplatin in mice].

The effect of root extract of Baikal skullcap (Scutellaria baicalensis) cultivated in vitro, on the gene structure of CBA/CaLac mice bone marrow cells damaged by anticancer drugs paclitaxel and cisplatin has been studied. It is established that the root extract exhibits gene protective property upon both single and chronic administration.

[Pharmacological correction of the cytogenetic effects of cisplatin].

Beginning with the first hours of experiments, cisplatin evoked an increase of chromosomal aberrations in CBA/CaLac bone marrow cells. Significant increase of structural infringements of chromosomes due to chromatid breaks was revealed in metaphase plates of murine bone marrow preparations through 24 h after cisplatin intraperitoneal introduction. In late terms of research (90th day), the high level of aberrations of chromosomes was retained. The most pronounced correction of cisplatin mutagenicity was achieved using a preliminary course of thiophan introduction.

Reaction of bone marrow hematopoiesis to the toxic effect of paclitaxel.

Intraperitoneal injection of paclitaxel (Mitotax) in a single dose of 40 mg/kg was followed by an increase in the number of mitotic granulocytic and erythroid cells, hypoplasia, and pancytopenia of the bone marrow in CBA/CaLac mice. The test preparation decreased the number of hematopoietic precursor cells for erythropoiesis and granulocytopoiesis, but increased the count of polyploid cells and incidence of structural and genomic abnormalities in bone marrow cells. These changes were reversible.

[Myelotoxicity of paclitaxel (mitotax)].

Paclitaxel (single intravenous injection in a maximum tolerated dose of 4.6 mg/kg) to white outbred rats causes bone marrow hypoplasia, increased granulocyte and erythroid cell mitosis (metaphase-anaphase transition), and moderate pancytopenia developments in peripheral blood (hypoplastic anemia, deep, short-term neutropenia, lymphopenia and thrombocytopenia) in the first hours after injection. A considerable increase of polyploidy (4n) cells and a moderate increase in the structural changes (chromatid deletions) of chromosomes was observed on bone marrow metaphase plates in 24 h. The drug introduction causes earlier increase in the rate of thymus cells mitosis, a growth in the number of thymocytes with apoptosis signs, and a moderate decrease in the thymus and spleen weight. All changes are reversible. Long-term (90 days after injection) observation revealed decreased lymphocyte count in the peripheral blood and bone marrow and earlier thymus involution.

Cytogenetic effects of antibodies to gamma-interferon in ultralow doses.

Single and course administration of ultralow doses of antibodies gamma-interferon did not increase the incidence of cytogenetic abnormalities in bone marrow cells from BALB/c mice and produced no genotoxic effect on Drosophila melanogaster wing cells in the test of somatic mosaicism.

Mutagenic activity of potentiated antibodies to erythropoietin.

Single and repeated administration of ultralow doses of antibodies to erythropoietin did not increase the count of aberrant metaphases in bone marrow cells of BALB/c mice and were not genotoxic for Drosophila melanogaster wing cells in the test of somatic mosaicism.

Early and delayed effects of carboplatin on the blood system.

Carboplatin injected intravenously in a maximum permissible dose to Wistar rats inhibited erythro- and granulocytopoiesis in the bone marrow, caused hyporegenerative anemia, leukopenia, and thrombocytopenia in the peripheral blood, led to hypoplasia of the thymus and spleen, and produced moderate apoptosis-inducing effects. These effects were observed within the first month after treatment. In mice carboplatin induced chromatid aberrations in the bone marrow and increased the count of erythrocytes with micronuclei. Moderate hypoplasia of erythro- and granulocytopoiesis and accelerated involution of the thymus were observed 3 and 6 months after cytostatic treatment. Our results indicate that carboplatin possesses higher myelotoxic activity compared to cisplatin.

[Myelotoxicity of epirubicin]. / O mielotoksichnosti épirubitsina.

Epirubicin (pharmorubicin, India), an antitumor antibiotic of the anthracycline group, was studied in regard to its effect on peripheral blood, bone marrow and lymphoid organs (the thymus and spleen) of CBA mice after its intraperitoneal administration in a single dose equal to the MIC (7.8 mg/kg) and in a course dose (1/5 of the MIC 5 times a day). The cytogenetic impairments induced by the cytostatic were estimated on metaphase plates with the bone marrow specimens and by counting the peripheral blood erythrocytes with micronuclei (the micronuclear test). It was shown that epirubicin induced cytogenetic disturbances in the hemopoietic cells within the first 72 hours. The antibiotic had a marked reversible effect on the erythroid population and lymphoid tissues and a moderate toxic action on the granulocyte population. The antibiotic did not affect thrombocytopoiesis. The single administrations had a more pronounced and prolonged myelotoxic and lymphotropic effect.