ABSTRACT
In this study hematological toxicity was analyzed after the single and repeated applications of tiazofurin (TZF). Cellularity of bone marrow, spleen and peripheral blood was examined, spanning the period of fifty days after the initial application. Analysis of hematological parameters was performed by slightly modified conventional techniques. The fraction of erythroid series was monitored during the experiment. Presented data describe kinetics of damage and recovery of hemopoietic tissue. Our results indicate that the effect of tiazofurin on cellularity of bone marrow and spleen and on erythropoiesis is reversible and dose dependent within tested dose range and therapeutic regimes. Twenty days after the application normal function of hemopoietic tissues was restored. This approach and results can be useful in defining the timing for sequencing and combination therapy with tiazofurin.
Subject(s)
Antimetabolites, Antineoplastic/toxicity , Blood Cells/drug effects , Erythropoiesis/drug effects , Ribavirin/analogs & derivatives , Alopecia/chemically induced , Anemia/chemically induced , Animals , Blood Cell Count/drug effects , Blood Cells/cytology , Bone Marrow Cells/drug effects , Cachexia/chemically induced , Cell Count/drug effects , Coma/chemically induced , Dose-Response Relationship, Drug , Hematocrit , Hemoglobins/metabolism , Lung/drug effects , Lung/pathology , Male , Rats , Rats, Wistar , Ribavirin/toxicity , Spleen/drug effects , Spleen/pathology , Splenomegaly/chemically induced , Survival RateABSTRACT
Effects of a modified CMF treatment on hematopoietic tissue and an implanted tumor were studied in rats. The modification of the treatment refers to the application of cyclophosphamide 24 h after methotrexate and 5-fluorouracil. The study was done on Wistar rats bearing Yoshida sarcoma in the ascites form. The controls were a) untreated animals bearing the tumor or b) treated conventionally with the 3 cytostatics and c) tumor-free animals under either conventional treatment or d) modified treatment. We examined survival, the appearance of metastases, and the regeneration of hematopoietic tissues. Improved survival, the absence of metastases, and improved regeneration of hematopoietic tissues was observed when modified CMF treatment was applied. These results support the importance of sequencing cytostatic protocols for basic hematological determinants and anti-tumor activity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Hematopoietic Stem Cells/drug effects , Sarcoma, Yoshida/drug therapy , Animals , Cyclophosphamide/administration & dosage , Drug Screening Assays, Antitumor , Female , Fluorouracil/administration & dosage , Methotrexate/administration & dosage , Neoplasm Transplantation , Rats , Rats, Wistar , Spleen/drug effects , Spleen/pathologyABSTRACT
Enhanced humoral, stimulating activities (HSAs) of post-cyclophosphamide (CY) sera and their purified fractions, acting on mitogen activated T-lymphocytes, were detected in Wistar rats after treatment by high single doses of the aplasia producing alkylating cytostatic drug CY. These activities, monitored in vitro, were partially purified from post-CY sera, collected 2, 4, and 7 days after treatment, yielding fractions with higher humoral stimulating activity. The preliminary purification included molecular cutting by Amicon-Diaflo filters (1-30 kDa pore size range) and gel-filtration on Sephadex G-50 and G-75. Results show that post-CY sera partially purified fraction (10-20 kDa), enhances the proliferation of hydrocortisone resistant (HCR) T-lymphocytes up to threefold under microculture conditions (P << 0.001); partially purified post-CY sera fraction (10-20 kDa) increases the proliferative response of T-cells in microcultures to the mitogenic 145-2C11 monoclonal antibody (mAb) up to tenfold (P << 0.001). These results show that the activity of stimulating factors is localized in the molecular weight range of 10-20 kDa.
Subject(s)
Blood Proteins/isolation & purification , Cell Division/drug effects , Cyclophosphamide/pharmacology , T-Lymphocytes/drug effects , Thymidine/metabolism , Animals , Blood Proteins/pharmacology , Cells, Cultured/drug effects , Cyclophosphamide/blood , Drug Resistance , Hydrocortisone , Male , Mice , Mice, Inbred C3H , Molecular Weight , Rats , Rats, Wistar , Spleen/drug effects , Thymus Gland/drug effectsABSTRACT
The effect of transplantation of Yoshida sarcoma cells into rats on the concentrations of both the acute-phase proteins (APPs) in the serum and their mRNAs in the liver has been investigated. In rats that responded to transplantation by forming solid tumors, the serum APP levels increased with tumor size. Some of the APP was found to be infiltrated in the area of the tumor cells. Concentrations of the APP mRNAs in the liver were enhanced to an extent comparable to that observed for the encoded proteins, indicating that hepatocytes were the major site of their synthesis. In rats in which no formation of solid tumors occurred, the serum APP concentrations expressed a tendency to decrease below the control values. An inverse relationship between the rates of APP synthesis and the capability of rats to prevent proliferation of transplanted ascites tumor cells in the solid tumor form was discussed.
Subject(s)
Acute-Phase Proteins/biosynthesis , Liver/metabolism , Sarcoma, Yoshida/pathology , Acute-Phase Proteins/metabolism , Animals , Blotting, Western , DNA/genetics , DNA Probes , Immunoelectrophoresis, Two-Dimensional , Male , Neoplasm Transplantation , RNA/genetics , RNA, Messenger/genetics , Rats , Rats, Inbred StrainsABSTRACT
The effect of total single fractionated irradiation with short time interval on haematopoietic regeneration of the bone marrow and spleen was investigated. Also, the importance of first dose, when dose of 600 R was divided in two unequal fractions with time interval of 300s was studied. The investigation was performed on 25 day old rats. The dose of 600 R (X-rays) was divided on: 500 + 100, 400 + 200, 300 + 300, 200 + 400 or 100 + 500 R with time interval of 150, 300 or 600s. Ten days after irradiation the changes in blood, bone marrow and spleen were observed. After unequal fractionated dose with interval of 600s slight effect was found. The results after intervals of 600s and 300s were significant, when the total dose was divided in two equal doses. The first dose has no promoting role in haematopoietic regeneration when total dose was unequally fractionated.
