Studies on the protective effects of Boerhaavia diffusa L. against gamma radiation induced damage in mice

The radioprotective effect of the hydro-alcoholic extract of Boerhaavia diffusa was studied using the in vivo mice model. The sublethally irradiated mice (600 rads, single dose) were treated intraperitoneally with 20 mg/kg of the extract. The animals were sacrificed at different time periods after the whole-body radiation. The most affected tissues--bone marrow and intestine--were considerably protected by the intraperitoneal administration of B. diffusa as estimated by bone marrow cellularity, maturing monocytes, and intestinal glutathione. Total white blood cell count was lowered drastically after radiation exposure (ninth day, 1500+/-500 cells/ mm(3)). When the animals were exposed to radiation and treated with B. diffusa, the total white blood cell count was lowered only to 4000+/-400 cells/mm(3) on the third day, and it reached an almost normal level (6250+/-470 cells/mm(3)) by the ninth day. The elevated level of serum and liver alkaline phosphatase after radiation exposure was reduced in the B. diffusa-treated group. The serum and liver glutamate pyruvate transferase, which were elevated after radiation exposure, were also reduced by treatment with B. diffusa compared to the control. The lipid peroxidation level also increased in the irradiated animals both in the liver and serum, but in B. diffusa-treated animals, there was a significant reduction in lipid peroxidation levels. The agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to gamma radiation showed heavy damage that was reduced by treatment with B. diffusa. These results are indicative of the radioprotective effect of the whole-plant extract of B. diffusa.     

Chemoprotective effect of Decalepis hamiltonii against cyclophosphamide induced toxicity

Cancer is a hyper-proliferative disorder that involves transformation, dysregulation of apoptosis, Proliferation, invasion, angiogenesis and metastasis. The conventional methods to treat cancer are surgery, radiotherapy and chemotherapy. Chemotherapy, being a major treatment modality used for the control of advanced stages of malignancies and as a prophylactic against possible metastasis, exhibits severe toxic side effects like diarrhea, fatigue, nausea, vomiting etc. Plants have been used for treating various diseases of human beings since time immemorial. In this study, methanolic extract of Decalepis hamiltonii was studied for its chemoprotective and antioxidant activity. Intraperitoneal administration of the extract significantly increased the total WBC count (3166 +/- 202 cells/cm2), bone marrow cellularity (680 +/- 70.1cells/femur), alpha-esterase positive cells (641 +/- 26.2 cells/4000 cells), Weights of organs such as a spleen and lungs, in Cyclophosphamide (CTX) treated animals when compared to control. D. hamiltonii administration significantly decreased the levels of Serum glutamate pyruvate transaminase (SGPT), Serum glutamate oxaloacetate transaminase (SGOT), creatinine and urea in serum and increased their levels in liver and kidney. Histopathological analysis of small intestine also suggests that extract could reduce the CTX induced intestinal damage. Analysis of the antioxidant status revealed that treatment with D. hamiltonii could significantly inhibit the free radical generation in vitro. Similarly in vivo studies using D. hamiltonii showed that the extract could significantly decrease the level of SOD in serum of the treated animals compared to control animals. In conclusion the finding of this study suggested that the extract from D. hamiltonii has strong chemo protective effect against CTX induced toxicity.     

Ameliorating Effects of Andrographis Paniculata Extract Against Cyclophosphamide-Induced Toxicity in Mice

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack of tumor specificity.Immunological and biochemical studies were here carried out to investigate protective effects of ethanolic extract ofAndrographis paniculata against cyclophosphamide (CTX) induced toxicity in vivo. Intraperitoneal administrationof the extract significantly increased the total WBC account (3256.5±196 cells/cm2), bone marrow cellularity(17.1±10.4x106 cells/femur) and β−esterase positive cells (849±23.2 cells/4000 cells) in CTX treated animals, whencompared to CTX alone treated control mice. Weights of lymphoid organs such as a spleen and thymus, reduced byCTX administration, were also increased by A paniculata treatment. Reduction of GSH in liver (4.8±0.21nmol/mgprotein) and in intestinal mucosa (13±0.67 nmol/mg protein) of CTX-treated controls was significantly reversed by Apaniculata administration (liver: 6.4±0.13, intestinal mucosa: 17.11±0.06), with amelioration of changes in serumand liver ALP, GPT, LPO (lipid peroxidation). Histopathological analysis of small intestine also suggests that extractcould reduce the CTX induced intestinal damage. The level of proinflammatory cytokine TNF-α, which was elevatedduring CTX administration, was significantly reduced by the A paniculata extract administration. The loweredlevels of other cytokines like IFN-γ, IL-2, GM-CSF, after CTX treatment were also found to be increased by extractadministration.     

Effects of prenatal irradiation on fetal, neonate, and young adult murine hemopoiesis

B6D2F1 mice received cobalt-60 radiation on day 10.5 of gestation at doses of 50 to 300 rad at a dose rate of 40 rad per min. These animals were studied at four selected age periods: (a) day 14.5 of gestation, (b) neonate, (c) juvenile, and (d) 13 week-old adult. Fetal liver cellularity, morphology, and hemopoietic progenitor cell concentration reflected injury after 200 rad. The 15 day-old mouse spleen cellularity was affected more than bone marrow cellularity, but greater radiation injury was reflected by bone marrow hemopoietic progenitor cells. Fluctuations from normal hematopoietic values were greater in the 15 day-old juvenile than in the 9 day-old neonate, commencing with 50 rad. These included peripheral blood parameters and marrow- and spleen-derived erythroid-, granulocytic- and megakaryocytic-progenitor cells. The consequences of prenatal irradiation (150 rad) were evident in the 13 week-old mouse. This was manifested by a reduced spleen cellularity and perturbations in concentrations of hemopoietic progenitor cells in the bone marrow.     

Effect in vivo of multiple injections of purified murine and recombinant human macrophage colony-stimulating factor to mice

Hematopoietic efficacy in vivo of multiple injections of purified murine L-cell and recombinant human macrophage colony-stimulating factors (M-CSF; specific activity, greater than 2 x 10(7) units/mg) was assessed in mice. Injections i.v. of sterile saline or 20,000 units of M-CSF were administered once (at 0 h), twice (at 0 and 12 h), or three times (at 0, 12, and 24 h) to C57BL/6 x DBA/2 F1 mice. Numbers and cycling rates of marrow and spleen granulocyte-macrophage, erythroid, and multipotential progenitor cells were assessed 32-36 h after the first injection. Marrow, spleen, and peripheral blood cellularity was assessed at intervals of up to 105 h. Progenitor cell cycling rates were significantly increased after one and two injections of M-CSF but were reduced to a slow or noncycling state after three injections. For marrow cells, the third injection resulted in a significant suppression of hematopoietic progenitor cell cycling compared to the control group. No significant changes were noted for number of progenitors per femur or spleen, for marrow, spleen, or peripheral blood cellularity, or for differential cell counts in these organs after any of the M-CSF treatment schedules. Suppression of progenitor cell proliferation noted after three injections of M-CSF may at least partially explain why repeated injections of 20,000 units of M-CSF fails to increase bone marrow, spleen, or blood cellularity even though one injection of M-CSF increases cycling rates of the hematopoietic progenitors.     

Immunomodulatory and Antitumor Activity of Biophytum sensitivum Extract

An alcoholic extract of Biophytum sensitivum was studied for its immunomodulatory and antitumor activity. Theextract was 100% toxic at a concentration of 0.5 mg/ml to Dalton’s lymphoma ascites (DLA) and Ehrlich ascitescarcinoma (EAC) cells. B. sensitivum extract was also found to be cytotoxic towards L929 cells in culture at aconcentration of 0.1 mg/ml. Administration of B. sensitivum extract (500μg/dose/animal) could inhibit the solid tumordevelopment in mice induced with DLA cells and increase the lifespan of mice bearing Ehrlich ascites carcinomatumors by 93.3%. B. sensitivum treatment significantly (p<0.001) reduced the tumor cell glutathione (GSH) levels aswell as serum gamma glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in ascites tumor bearing animals.The total WBC count was also increased to 14,087 cells/mm3 on the 12th day in BALB/c mice. The number of plaqueforming cells also enhanced significantly (p<0.001), and bone marrow cellularity and β-esterase positive cells werealso increased by the administration of B. sensitivum extract.     

Mortality of radiation chimeras in relation to the number of transplanted bone marrow and lymph node cells

Injection of lymph node cells along with therapeutic doses of bone marrow cells into irradiated animals can cause death if the lymphoid cells are capable of reacting against the host animal. The mortality and time of death are proportional to the number of lymphoid cells injected. Death can be as late as 70 days after irradiation. Injection of bone marrow cells alone can cause death but only when very large numbers of cells are given and only in certain donor-host combinations. Great numbers of bone marrow cells raise the death rate after injection of lymph node cells in certain donor-host combinations but counteract this killing effect in other combinations. The number of immunologically competent cells in bone marrow from both CBA and C57BL mice is small. In CBA mice an equivalent number of immunologically competent cells was estimated in 20 x 10(6) bone marrow and in 0.05 to 0.1 x 10(6) lymph node cells; for C57BL mice these figures were 50 x 10(6) bone marrow and 0.4 x 10(6) lymph node cells. To explain why bone marrow can apparently offset the killing effect of lymphoid cells, it is postulated that immunologically tolerant cells developing from pluripotent stem cells in bone marrow compete with immunologically competent lymphatic cells.     

Increased Protective Effect of Cystamine and Mexamine Against Radiation after Activation of the Haemopoiesis by Dextran Sulphate in Mice

The effect gained by activation of haemopoietic cell populations by a single injection of dextran sulphate (DS) on the protective effect of cystamine and mexamine administered in small doses was monitored in mice. On irradiation 24 hours after the injection of DS the number of endogenous spleen colonies increased following the administration of mexamine and cystamine, the number of haemopoietic stem cells surviving in the femur after irradiation increased, and recovery of the cellularity of irradiated bone marrow was accelerated. Both substances administered 24 hours after the injection of DS significantly reduced the lethal effects of gamma rays. The maximum values of the dose reduction factor, for combined radiation protection, reached 1.48 as regards decreased lethal effects and 1.6 as regards equieffective E-MSC exposure.     

Fatal polycythemia induced in mice by dysregulated erythropoietin production by hematopoietic cells.

C57BL/6J murine bone marrow cells, infected with a retroviral vector (MP Zen) carrying a monkey erythropoietin cDNA, were transplanted into lethally irradiated syngeneic recipients to study the effect of erythropoietin production by hemopoietic cells. High levels of erythropoietin were recorded in the plasma (median value: 1.2 u/ml) and in media conditioned by peritoneal, spleen, and bone marrow cells from recipient mice. In transplanted mice, the hematocrit was elevated (90 +/- 5%) and the mice died at a mean of 71 days after transplantation. In the blood, platelet counts were usually low and nucleated blood cells slightly elevated. Spleen weight increased 5-fold and bone marrow cellularity decreased slightly. There was a 9.9-fold increase in erythroblast numbers, a 2-fold reduction of lymphocytes, and no variation of the myeloid cells when the total cellularity of bone marrow, spleen, peripheral blood, and peritoneal cells were considered. Calculation of the total numbers of progenitor cells in these organs revealed a 18-fold increase in erythroid colony-forming units (CFU-E) but no significant variation of the erythroid burst-forming units (BFU-E), and myeloid progenitor cell numbers. A variable proportion of CFU-E, (12% or 24% in bone marrow or spleen, respectively) was able to proliferate in unstimulated cultures. Erythropoietic amplification occurred in the spleen and there was a redistribution of the BFU-E and myeloid cells from the bone marrow to the spleen. No significant extramedullary erythropoiesis was seen. This study emphasizes the erythroid specificity of erythropoietin and shows that elevated dysregulated erythropoietin production by hemopoietic cells leads to a fatal polycythemia without erythroid neoplastic transformation.     

Stimulatory Effect of Intermittent Feeding on Hemopoietic Recovery in Sublethally Gamma-Irradiated Mice

The effect of three-week adaptation to intermittent feeding on the recovery of the hemopoietic functions of mice after sublethal gamma irradiation was investigated. Measurement of oxygen consumption, carbon dioxide output and the respiratory quotient demonstrated an increased metabolic rate in the intermittently fed animals and an accentuation of lipogenic processes. This metabolic state persisted even after irradiation. An improvement in the recovery of hemopoietic functions after irradiation was demonstrated in adapted animals, which was reflected by the increased proliferative activity of the hemopoietic cell populations (more intensive incorporation of ¹²⁵J-UdR into the DNA of cells of the spleen, thymus and femoral bone marrow), by more rapid renewal of spleen weight, more rapid recovery of the femoral bone marrow cellularity and increased levels of granulocytes in peripheral blood.     

Diethyldithiocarbamate inhibition of murine bone marrow toxicity caused by cis-diamminedichloroplatinum(II) or diammine-(1,1-cyclobutanedicarboxylato)platinum(II)

We report here the effects of diethyldithiocarbamate (DDTC) rescue on myelotoxicity caused by carboplatin (CBDCA) and cisplatin (DDP) in C57BL/6 x DBA/2 F1 mice. All drugs were administered by injection into the tail vein. Myelotoxicity was assessed by WBC, bone marrow cellularity, and assays for pluripotent bone marrow stem cells (spleen colony forming unit) and granulocyte/macrophage progenitor cells (granulocyte/macrophage colony forming unit in culture). The most significant protection occurred in stem cells, where a single dose of DDTC (300 mg/kg) produced a platinum-drug dose modification factor of 3.3; i.e., the addition of DDTC reduced stem cell toxicity to the level produced by approximately one-third the dose of platinum drug alone. On a molar basis, DDP was 2.4 times as toxic to stem cells as CBDCA. The response of the stem cells to CBDCA and DDP was linear both with and without rescue, and the dose modification factor remained constant for doses of CBDCA up to 120 mg/kg and doses of DDP up to 15 mg/kg. Moreover, stem cell rescue appeared to be independent of DDTC dose (100-750 mg/kg) and time of administration (1.5 h before to 5 h after platinum drug). DDTC protection was less impressive for more mature hematological cells (granulocyte/macrophage colony forming units in culture). In studies of bone marrow cellularity, addition of DDTC (300 mg/kg) to DDP treatment (10 mg/kg) produced a 50% increase in the granulocyte-predominant cell population but had no effect on the lymphocyte population. Peripheral WBC showed no significant difference between rescued and unrescued groups and did not reflect the toxicity observed directly in the bone marrow.     

Haematopoietic late effects of prolonged bleomycin treatment in mice

Summary In two studies, haematopoietic late effects of prolonged bleomycin treatment were evaluated in mice given serial injections of 21 mg bleomycin/m² weekly for 31 and 44 weeks, respectively. Femoral bone marrow cellularity measured at 43, 45, and 49 weeks after discontinuation of the drug in the first and after 20 weeks in the second study was found to be significantly (P<0.05) lower in the treated mice than in the controls. CFU-S, BFU-E, and CFU-C contents were also reduced in the treated bone marrow, but with the exception of CFU-S in the second study, differences from control values were not significant. Additional long-term bone marrow cultures performed in the second study revealed no marked changes in the marrow proliferative activity and the self-renewal of stem cells to explain the reduced marrow cellularity and stem cell content. These last findings might, therefore, be due to a decrease in femoral size with less marrow content in the treated mice, since measurements of the tibial weights in both groups showed that the bones in the treated animals were significantly (P<0.05) lighter than those in the controls.     

Cardiospermum halicacabum inhibits Cyclophosphamide Induced Immunosupression and Oxidative Stress in Mice and also Regulates iNOS and COX-2 Gene Expression in LPS Stimulated Macrophages

The effect of a methanolic extract of Cardiospermum halicacabum L was studied against cyclophosphamide(CTX)-induced toxicity in mice. Administration of CTX (25 mg/kg b.wt, i.p.) for 10 days produced significantmyelosuppression as evidenced by a decreased WBC count and bone marrow cellularity. Co-treatment withCardiospermum significantly increased the total WBC count, bone marrow cellularity and α-esterase positivecells, and the relative organ weights of spleen as well as thymus compared to the CTX alone treated group.Cardiospermum further reduced the enhanced levels of ALP, GPT, LPO, and proinflammatory cytokine TNF-α,and also significantly increased the glutathione (GSH) level in CTX treated animals. The lowered levels ofother cytokines like IFN-γ, IL-2, GM-CSF, after CTX treatment were also found to be increased by extractadministration. Histopathological analysis of small intestine also suggested reduction of CTX-induced intestinaldamage. Moreover the extract down-regulated the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2(COX-2) mRNA expression in LPS stimulated macrophages. These studies indicate that C. halicacabum couldreduce cyclophosphamide induced oxidative stress and immunosupression through enhancing the antioxidantstatus and immunomodulation by stem cell proliferation.     

Acute myelofibrosis: response to recombinant human interferon alpha-2a

Acute myelofibrosis is a rare myeloproliferative syndrome characterized by bone marrow proliferation of atypical megakaryocytes, poor response to conventional leukemic therapy, and a fulminant clinical course. Because alpha interferon exhibits potent antiproliferative effects against megakaryocyte progenitors and human fibroblast cell lines, we treated two patients with acute myelofibrosis or the related syndrome of acute myelodysplasia with myelofibrosis with recombinant human interferon alpha-2a. Patient 1 received a 12-week course of interferon alpha (1-6 x 10(6) IU/d) after failure of two cytarabine-based chemotherapy regimens. Interferon administration resulted in prompt improvement in symptoms, stabilization of leukocyte count, and a reduction in circulating blast forms. Primary treatment with interferon (1-3 x 10(6) IU/d x 4 weeks) in patient 2 produced complete hematologic recovery with restoration of marrow cellularity and reduced marrow fibrosis. Our findings suggest that interferon alpha may have significant activity in the treatment of patients with acute myelofibrosis.     

Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model

PURPOSE: To compare the efficacy of autologous cell therapy after irradiation combined with granulocyte-colony stimulating factor (G-CSF) injections with G-CSF treatment alone in a heterogeneous model of irradiation representative of an accidental situation. MATERIAL AND METHODS: Non-human primates were irradiated at 8.7 Gy whole-body dose with the right arm shielded to receive 4.8 Gy. The first group of animals received G-CSF (lenograstim) injections starting 6 h after irradiation, and a second group received a combination of G-CSF (lenograstim) injections and autologous expanded hematopoietic cells. Animals were followed up for blood cell counts, circulating progenitors, and bone marrow cellularity. RESULTS: No significant differences were seen between the two treatment groups, whatever the parameter observed: time to leukocyte or platelet recovery and duration and severity of aplasia. CONCLUSION: Our results indicated that identical recovery kinetic was observed when irradiated animals are treated with G-CSF independently of the reinjection of ex vivo expanded autologous hematopoietic cells. Thus G-CSF injections might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims.     

Demand-control of proliferative activity in the hemopoietic system of lethally irradiated mice during transfusion-induced regeneration

The extent of cell proliferation in the hemopoietic system after bone marrow transfusion of fatally irradiated mice depends on the regeneration of proliferative capacity. This may be modified by the demand for differentiated cells in the peripheral blood. This demand was suppressed by induction of transfusion plethora prior to 800 rad whole body irradiation and bone marrow transfusion. Controls were non-plethoric recipients. For 6 days the following parameters were measured: hemopoietic proliferation by the 125-iodo-deoxyuridine (125-IUdR) incorporation technique, CFU-S content and spleen colony histology. There are three general observations from spleen and marrow with respect to 125-IUdR uptake in plethoric mice: (1) initial higher 125-IUdR uptake, (2) reduced rate of increase of 125-IUdR incorporation, (3) this rate of increasing 125-IUdR uptake in spleen was more depressed than in marrow. On day 6 cellularity and CFU-S in spleen was below, and in marrow above that of the control. These data suggest that initially after fatal irradiation of control mice differentiation of transfused CFU-S predominates over proliferation. Later as the mice become anemic and erythropoietin is produced the stimulation to proliferate is greater in the control than in the plethoric mice in which erythrocytic proliferation is suppressed. These data suggest that there are multiple feedback loops that regulate regeneration in the spleen and the bone marrow. These differences may be connected with the microenvironment that preferentially initiates erythropoiesis in the spleen before the marrow and granulopoiesis in the marrow before the spleen.     

Enhancement of murine bone marrow ablation by combining whole body hyperthermia with total body irradiation and cyclophosphamide

Bone marrow ablation using combined whole body hyperthermia (WBH), total body irradiation (TBI), and cyclophosphamide (Cy) was investigated in C3H f/Sed mice to demonstrate cytotoxic synergism between the three modalities. TBI was given on day 0. WBH treatment was for 1 hr at 41.8 degrees C, given in daily sessions for 1, 2 or 3 modalities. TBI was given on day 0. WBH treatment was for 1 hr at 41.8 degrees C, given in daily sessions for 1, 2 or 3 consecutive days following TBI. Total cyclophosphamide doses were 160 and 240 mg/kg given in 2 daily injections on days 1 and 2 following TBI. Polymorphonuclear leukocyte and lymphocyte numbers were determined by differential cell counts. The total peripheral blood cell counts were also determined. WBH alone, given in daily sessions for 3 days, did not reduce the total peripheral blood cell counts. However, when WBH was added to TBI (6.3 Gy) peripheral blood cellularity was reduced on day 2, but no significant heat/radiosensitization was evident after day 2. WBH (3 daily sessions) significantly reduced the peripheral blood cellularity and resulted in bone marrow ablation when it was combined with TBI and Cy. CY (160-240 mg/kg) combined with TBI (5.4 Gy) resulted in bone marrow ablation and subsequent death in 14-22% of mice treated; 60-100% of mice died from bone marrow ablation when WBH was added to TBI (5.4 Gy) and Cy (160-240 mg/kg). Femoral and vertebral tissue sections showed total loss of progenitor cells when WBH, TBI (5.4 Gy), and Cy (240 mg/kg) were combined whereas lessor treatment was associated with histologically verified reconstitution of progenitor cells inside the marrow cavities. These studies indicate that bone marrow ablation can be achieved when using WBH in combination with lower doses of TBI and Cy.     

Clastogenic Potential of Ruta graveolens Extract and a Homeopathic Preparation in Mouse Bone Marrow Cells

Ruta graveolens belonging to family Rutaceae has long been traditionally used as a medicinal plant as well asa flavoring agent in food. However, very little data are available on the toxicity of the plant. This report presentsevidence on the genotoxic and clastogenic potential of an extract of Ruta graveolens and Ruta 200C, a homeopathicpreparation. Various types of chromosomal aberrations were noted in bone marrow cells after treatment. Thepercentage of aberrated cells in 4the 00mg/kgb.wt extract administered group was found to be 21% and with1000mg/kg.b.wt it was 31%. The 23% for the Ruta 200C treated group was also elevated as compared to the3%for untreated animals. In addition, bone marrow cells had higher incidence of micronuclei induction whentreated with the extract (400mg and 1000mg/kg body weight) and 20μl/animal Ruta 200C for 30 days.Administration of the extract (1000mg/kg.b.wt) over a period of 30 days also resulted in damage to cellular DNAas evidenced by comet formation where the comet parameters such as percentage DNA in tail, tail length, tailmoment of the bone marrow cells were increased several fold over control values. The comet tail moment of thebone marrow cells increased from 4.5 ± 2.5 to 50.2 ± 25.2 after the extract treatment. Administration of 20μl/animal Ruta 200C for 5 consecutive days increased the tail moment to 11.7 ± 2.9. These results indicate that Rutagraveolens and Ruta 200C may induce genotoxicity in animals.     

A practical miniature long-term bone marrow culture system for investigating early myelodysplasia.

A method was devised to grow haemopoietic cells in long-term bone marrow culture (LTBMC) which requires only 1 x 10(6) cells/culture. Such miniature cultures were used to study growth patterns of marrow from patients with myelodysplastic syndromes (MDS). Consistent differences in LTBMC cellularity and cellular composition were noted between MDS and normal marrow. These differences were accentuated by rGM-CSF. The criteria which distinguished between and MDS marrows were: cell count at weeks 1 and 4, % neutrophils and % blasts. In 10 patients with unexplained macrocytosis or pancytopenia miniature LTBMC results clearly segregated into either 'normal' or 'MDS' growth patterns. Miniature LTBMC with rGM-CSF may therefore be a useful diagnostic test for early MDS.     

Effects of interleukin 2 on engraftment following autologous bone marrow transplantation (ABMT) in dogs.

Beagle dogs were treated with recombinant human interleukin 2 (IL-2) 6 x 10(6) International Units (IU)/day for 7 consecutive days following conditioning with sublethal (200 cGy) or lethal (400 cGy) doses of high-dose rate whole body irradiation (WBI) and reconstitution with 2 x 10(8)/kg autologous bone marrow cells, in order to assess the effect of IL-2 on engraftment. Engraftment of dogs conditioned by lethal doses of WBI was not impaired following treatment with IL-2 6 x 10(6) IU/day. At an RIL-2 dose of 6 x 10(6) and 9 x 10(4) IU/day, enhanced engraftment of autologous bone marrow cells was observed in dogs irradiated with a sublethal WBI dose in comparison with controls not treated by IL-2(p < 0.05). We conclude that therapeutic doses of IL-2 may be safely utilized during hematopoietic reconstitution. Under certain conditions IL-2 may even enhance hematopoietic reconstitution following ABMT.