Irradiated Guinea Pigs Research Articles

Effect of The Rs-10 Radioprotector on Protein-Steroid Interaction in Irradiated Animals with Biphasic Adrenocortical Response to Irradiation

The article is devoted to the influence of RS-10 radioprotector on the protein-steroid interaction in irradiated animals. Introduction. Increasing threats to the radiation safety of the population is now causing the need for comprehensive studies of the anti-beam properties of chemical radioprotectors. The aim of the study is to study the effect of the RS-10 radioprotector on protein-steroid interaction in irradiated guinea pigs with biphasic adrenocortical response to irradiation. Study methods: experiments were conducted on 146 guinea pigs weighing 300-350 g, which were exposed to total ƴ radiation at a dose of 3.5 Gy and 4.5 Gy at a dose rate of 5.76 Gy/min, which caused them radiation disease of II and III severity. Experimental animals were injected intraperitoneally with RS-10 (chitosan bitartrate) 15 minutes before irradiation. Control animals were administered an equal volume of saline. The total plasma content of 11-oxycorticosteroids (11-OKS) was determined by the fluorometric method of Guillemin et al. in the author's modification. The binding capacity of corticosteroid binding globulin (CSG) was determined by gel filtration of De Moor at al. in the author's modification. Conclusions. Prophylactic administration of RS-10 to irradiated animals with a two-phase adreno-cortical reaction to radiation causes a later onset of secondary hypercorticism in the midst of radiation sickness in animals. Prophylactic administration of RS-10 before irradiation reduces the level of free hormone and leads to a decrease in hypercorticism, increasing the reserve capabilities of the binding ability of the CSG at the height of radiation sickness. A leading role in the mechanism of reducing affected hypercorticism under protective conditions has a lesser degree of impairment of the binding capacity of the CSG, rather than a change in the total level of 11-OKS in the blood.

Cobalt-60 lymphocytes immuno-phenotypes/myeloid-lymphoid toxicities and countermeasure effects of aqueous extracts of Parquetina nigrescens, Camellia sinensis and Telfairia occidentalis in guineapigs

Introduction: Radiotherapy is an outstanding and efficacious mode of cancer management. Immune dyscrasia and dyshaemopoiesis in patients being managed with radiotherapy are well documented. Currently, no ideal radio-immuno-haematologic countermeasures in clinical use especially because, of their toxicities at the optimal concentrations exists. This study assessed the countermeasure effects of Parquetina nigrescens, Camellia sinensis and Telfairia occidentalis on immune syndrome in irradiated guineapigs. Methods: Thirty guineapigs were randomly assigned to nine groups: [A1-A4 (Pre), B1-B4 (Post) and C (Control)] where (n = 3)/group for countermeasure studies. Animals were exposed to 4.0 Gy whole-body Co60 while extracts were administered twice daily at concentrations of 400 mg/ml, 1000 mg/ml, 900 mg/ml of C. sinensis, P. nigrescens and T. occidentalis respectively. Peripheral whole blood was collected on days (D): baseline, D0 [24 hours after radiation], D3, D9 and D14. Haemogram and CD4 were analyzed. Results: Lymphocyte immune-phenotypes (CD4, Twbc), Abs. Neutrophil and Neutrophil:Lymphocyte ratio (NLR) counts were significantly increased from day 3 to 14 except NLR that was erratic on day 14 (p = 0.01). Contrarily, Absolute Lymphocyte counts were significantly decreased from day 3 to 9 then increased significantly on day 14 (p = 0.00) with significant NLR similarly on day 14 (p = 0.02). Conclusion: The results indicate a significant decrease in lymphocyte-immunophenotypes in group C as compared to groups A and B, suggesting that extracts showed significant ameliorating effects in groups A and B probably by minimizing the activation of ROS/NOS. The leaves’ extracts of Camellia sinensis, Parquetina nigrescens and Telfairia occidentalis showed potent counter-effects to radiation-induced haemopoietic and immune dyscrasia syndromes in guineapigs.

Penicillamine as radiation protector against gamma radiation effect on complete blood count parameters of guinea pigs

Background and aim The increasing use of nuclear technology has increased the risk of exposure to radiation. Exposure to radiation induces harms to human beings. The blood and blood-forming organs are one of the most sensitive to radiation. People exposed to high radiation doses had blood count changes, and death may occur owing to acute radiation syndromes. Therefore, radioprotective compounds are very important in clinical radiotherapy. The aim of this study was to examine the effect of penicillamine as a radiation protector agent against gamma radiation effects on complete blood count parameters of guinea pigs. Materials and methods Thirty healthy male guinea pigs were divided into three equal groups: treated irradiated (n=10), irradiated (n=10), and control (n=10) groups. The treated irradiated and irradiated groups were exposed to acute gamma radiation dose (9 kGy). The treated irradiated group received penicillamine (10 mg/kg) 1 h before exposure to radiation. Blood samples were collected soon after radiation and immediately placed in tubes containing EDTA, and these samples were used in the assessment of blood profile. Results Treated irradiated guinea pigs had significant higher red blood cell count, white blood cell count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration (P≤0.05). The treated irradiated guinea pigs had significant lower relative distribution width of red blood cells by volume coefficient of variation (%) and platelet count (P≤0.05). Relative width of the distribution of platelets in volume index of the heterogeneity of platelets (%) had no significant difference between the two groups (P>0.05). Conclusion Administration of penicillamine reduced radiation damage to red blood cell count, white blood cell count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration.

Proliferative Effect of Aqueous Extracts ofParquetina Nigrescens on HaemopoieticMultipotent Stem Cells in Irradiated Guinea Pigs

Patients suffer a decrease in haemopoietic stem cells as a consequence of disease, radiation or chemotherapy. Radiotherapy and chemotherapy are common therapeutic modalities for cancer, leukemia, and lymphoma. Unfortunately, these therapies are not tumor-specific. Normal tissues, particularly the bone marrow (BM), are extremely vulnerable to cytotoxicity caused by these therapies. Antidotes are required for the untoward side effects of these therapies. Although a lot of potential better treatments are currently being developed, few research studies have investigated the proliferative effect of plant extracts which may modulate stem cells self-renewal and differentiation. However, in recent years there has been an upsurge of interest on the effects of various dietary insufficiencies on haemopoietic and immune responses (Sanberg et al., 2006). Other investigators have recently reported that dietary fatty acids, particularly oleic acid and linoleic acid, actively promote the proliferation of haemopoietic stem cells (Sanberg et al., 2006) as well as modulate the self-renewal of intestinal epithelial cells. This study was done to determine the potential proliferative effect of Parquetina nigrescens on haemopoietic multipotent stem cells in irradiated guinea pigs bone marrow. The study shows that the plant has positive proliferative effects on haemopoietic multipotent stem cells. The proliferative effect correlates with the concentration of the P. nigrescens.

Effect of a single dose of a bradykinin potentiating factor isolated from scorpion venom (Buthus occitanus) on total protein and albumin in serum of irradiated growing male Guinea pigs.

Whole body gamma irradiation of growing male Guinea pigs at the dose of 150 rads/animal reduced the levels of total protein and albumin. Growing Guinea pigs males (250 ± 30 gm. b. w.) were divided into two main groups; non-irradiated and irradiated groups and every main group were divided into four sub-groups. Irradiated growing Guinea pigs males groups were exposed to 150 Rads/animal by cesium-137 irradiation unit with a dose route of 1.06483 rad per second in a uniform manner and divided into four sub-groups. In irradiated groups; the first sub-groups were interaperitoneally (i.p) injected with100 µL saline solution. The second sub-groups were i.p. injection of bone marrow cells from their twins (2.5x10 6 cells/animall). The third sub-groups injected i. p with BPF (1µgm/gm. b. w.) which was dissolved in saline solution. The fourth sub-group injected with i.p solution of BPF (1µg/gm. b. w.) together with bone marrow cells from their twins (2.5x10 6 cells/animal). The nonirradiated sub-groups were injected with the same manner of irradiated sub-groups. The level of total protein and albumin in serum were measured at periods of 1, 3, 7, 14 and 21 days. Irradiated animals i.p. injection of BPF (single dose); appears slight to improve the changes which occurred in both total protein and albumin compared to irradiated sub-group. However, irradiated Guinea pigs injected with single dose of BPF together with bone marrow cells were more improvement of these parameters than sub-groups injected with only single dose of BPF. The improvement of these parameters may be attributed to stimulate growth factors and/or growth hormones to increase protein synthesis as an effect on the liver that necessitates future investigations.

Analysis of the Cytoprotective Effect of Amifostine on the Irradiated Inner Ear of Guinea Pigs: An Experimental Study

SummaryRadiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors.Aimthe objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region.Materials and MethodsAn experimental study conducted on four groups of guinea pigs were used; One group received only amifostine, one group was submitted to a single dose of 350 cGy and the other two were similarly irradiated but received amifostine doses of 100 or 200 mg/kg. All animals were slaughtered 30 days after the experiment, their bullae were removed and the damaged outer hair cells were counted.ResultThe extent of injury was lower in the outer hair cells of the two groups treated with amifostine compared to the group that was only irradiated. There was no difference between the group treated with 100 and 200 mg/kg of amifostine. The group that received only amifostine had no cochlear damage.ConclusionAmifostine is an effective cytoprotective substance in the Organ of Corti of irradiated guinea pigs.

Study on anti-inflammatory effects of silymarin on UV irradiated guinea pig skin

Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation as a tumor initiator, tumor promoter and complete carcinogen, and excessive UV exposure can lead to the development of various skin disorders including melanoma and non-melanoma skin cancers [1]. Considering skin damages due to UV irradiations of the sun and need of UV-protective products, we investigated the efficacy of silymarin to prevent the side effects of these rays. For this survey 120 albino guinea pigs, in the same age and sex were selected and randomly divided into four groups with thirty animals in each group. The skin of the lumbar region of each animal was shaved. Experimental group 1 received 9mg silymarin in 20µl acetone topically while control group 1 received only 20µl acetone topically. Experimental group 2 received 50mg silymarin orally and finally the control group 2 received nothing [2]. The light type was UV-B, 220V, 30W, with the dose of 180mj/cm2. The results of clinical and pathological observations showed that silymarin in topical and oral use resulted in a significant decrease (79% and 67% respectively) in pathological damage incidences of skin due to UV irradiation. Oral and topical use of silymarin significantly reduced the side effects of UV irradiation and it can be used in topical ointments as well.

Enhancement of platelet recovery in X-irradiated guinea pigs by romurtide, a synthetic muramyl dipeptide derivative

The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose- dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Enhancement of Platelet Recovery in X-Irradiated Guinea Pigs by Romurtide, a Synthetic Muramyl Dipeptide Derivative

AbstractThe response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 µg/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 µg/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose-dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 µg/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

GUINEA-PIG SPINAL-CORD AS A MODEL FOR THE STUDY OF LATE RADIATION-INJURY AND REPAIR

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.

Mammary gland tumors in irradiated and untreated guinea pigs.

This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.

A reliable method for reconstituting thymectomized, lethally irradiated guinea pigs with bone marrow cells

We developed a reliable method for reconstituting thymectomized, lethally irradiated guinea pigs. Injection of 2.5 − 10 × 10 7 syngeneic bone marrow cells into adult thymectomized, lethally irradiated guinea pigs produced survival of 46–100% of treated animals. Gentamycin sulfate (5 mg/kg of body weight) for 10 days was required for optimal results. Acidified drinking water (pH 2.5) appeared to be required for optimal results. Thymectomized, lethally irradiated, bone marrow reconstituted (‘B’) guinea pigs had impaired ability to develop delayed cutaneous hypersensitivity to mycobacterial antigens and cutaneous basophil hypersensitivity to keyhole limpet hemocyanin; proliferative responses to phytohemmagglutinin were impaired.

Changes in cellular DNA sequence adjacent to integrated viral genome in transplantable and nontransplantable guinea pig cells transformed by SV40.

Guinea pig (strain No13) kidney cells were transformed with SV40 (SVNo13). When this transformant was injected subcutaneously into syngeneic irradiated guinea pigs, tumors were produced in some animals. One of them became transplantable (ST13). Clones were obtained from cultured tumor cells (STC13). About one copy of the viral genome appeared to exist in both SVNo13 and STC13 clones as determined by reassociation kinetics. We have examined the distribution of integrated viral sequences in the host DNA by blot hybridization. In SVNo13, the blotting pattern with BamHI showed two main bands of 6.9 and 4.3 kilobases (kb), whereas in STC13 clones the 6.9-kb band was replaced with a shorter one of 6.1-kb. The blotting pattern with EcoRI also showed distinct changes between SVNo13 and STC13 clones. These results suggest either the occurrence of some mutations or deletions in the cellular DNA adjacent to the integrated viral genome or the transposition of viral DNA sequences during tumor development.

Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells.

Primary Tumors and Adenomatosis Of The Lung In Untreated and In Irradiated Guineá Pigs

The morphology of alveologenic tumor, hemangiosarcoma, lymphangioma, intrabronchial papilloma and adenomatosis observed in the lung of guinea pigs is described. Electron micrographs revealed alveologenic tumor to consist of Type II pneumocytes and the lesion of adenomatosis to consist of distended alveoli lined with ciliated bronchial type epithelial cells. A relationship between the dose of gamma or X-ray irradiation received and the frequency of guinea pigs with lung tumors could not be established. In guinea pigs, which survived over 20 months, the frequency of alveologenic tumors in the inbred strains was 23/107 in irradiated and 11/79 in untreated guinea pigs; this difference was statistically not significant. The frequency of tumor bearing inbred males (11/60) was significantly lower than of tumor bearing noninbred males (23/65). In the irradiated guinea pigs alveologenic tumors occurred earlier and tumor nodules in the lung were more numerous than in the untreated guinea pigs. Primary hemangiosarcoma involved the lung of one untreated and one irradiated strain 2 guinea pig. A single lymphangioma was found in an untreated inbred guinea pig. Intrabronchial papillomas were observed twice in irradiated and once in untreated guinea pigs. Adenomatosis was present in the lung of 2 untreated inbred and 5 irradiated noninbred guinea pigs.

Cell membrane mechanisms of action of prostaglandins E1 and F2? on platelet function

The influence of gamma-rays 60Co and fast neutrons on intravascular platelet aggregation and prostacyclin activity of the vascular wall has been studied. It has been shown that 1-6 hours after irradiation of CBA mice, a great number of bone marrow platelets clump to form fibrin fibrils that often close completely the vascular lumen. Experiments with irradiated rats and guinea-pigs have demonstrated the reduction of prostacyclin-like activity in the abdominal aorta wall.

Differential Growth of Allogeneic Bone Marrow and Leukemia Cells in Irradiated Guinea Pigs

Abstract Growth of normal bone marrow and L2C leukemia cell grafts was studied in lethally irradiated strain 2 and strain 13 guinea pigs by measuring 125IUdR uptake in the spleen and bone marrow and by histologic examination of these tissues. Allogeneic bone marrow cells proliferated as well as syngeneic cells in both strain 2 and 13 animals. Since strains 2 and 13 guinea pigs differ only at the I region of the major histocompatibility complex, this observation indicates that Ia disparities are not relevant to marrow graft rejection in the guinea pig. Both Ia positive and Ia negative L2C leukemia cells of strain 2 origin grew well in the spleen of irradiated strain 2 animals. However, irradiated strain 13 animals showed considerable resistance to the growth of both leukemia cell lines. F1 hybrids (2 × 13) also showed resistance to the growth of the leukemia cells, although resistance was less than in strain 13 animals. These observations suggest the existence of an effector system capable of mediating natural resistance to L2C cells in unimmunized strain 13 and F1 guinea pigs. The nature of antigens recognized by these radiation resistant effector cells are not entirely clear. However, Ia antigens, or tumor-associated antigens dependent upon Ia antigens for immunogenicity, do not seem to be the primary targets in this phenomenon.

Adenocarcinoma of the Gallbladder in Guinea Pigs

Adenocarcinoma of the gallbladder developed in 17 of 68 untreated and in 26 of 83 irradiated guinea pigs of inbred strains 2 and 13. The carcinomas spread widely by direct extension and through lymphatic and blood vessels to lymph nodes, mesenteries, omenta, abdominal wall, liver, lungs, bones, and spleen. Whole-body exposure to gamma or X-radiation increased both the number of tumors and metastases in male inbred guinea pigs but not in females. Significantly fewer (9 of 98) noninbred than inbred guinea pigs developed gallbladder carcinomas after irradiation. In 9 untreated noninbred guinea pigs gallbladder carcinomas were not found. Inasmuch as the effect of irradiation was not dose-dependent, an indirect systemic effect of irradiation was postulated. This is the first report on the occurrence of spontaneous gallbladder adenocarcinomas in guinea pigs.

Studies on the pathogenesis of experimental autoimmune renal tubulointerstitial disease in guinea pigs: II. Passive transfer of renal lesions by anti-tubular basement membrane autoantibody and nonimmune bone marrow cells to leukocyte-depleted recipients

Renal tubulointerstitial disease (RTD) in guinea pigs is induced by anti-tubular basement membrane (TBM) antibodies, complement, and radiosensitive mononuclear cells. The present experiments show that the bone marrow is the source of the initial cellular infiltrate. Groups of normal and irradiated guinea pigs were passively immunized to TBM; in addition, some of the leukocyte-depleted passive transfer recipients were injected with bone marrow cells from unimmunized donors. By day 6–8 RTD had occurred in 36 of 36 unmanipulated recipients, in none of 45 depleted animals, and in 18 of 25 given a combination of marrow cells and antibody. Under similar conditions, irradiated marrow cells or viable cells from thymus, spleen or lymph node did not elicit the accumulation of mononuclear cells in the renal cortex. Hence, mononuclear cells derived from the bone marrow play a major role in the pathogenesis.

Synthesis of C4 by C4 Deficient NIH-Albany Strain Guinea Pig Radiation Chimeras: Restoration of the Classical Pathway of Complement

Abstract We have detected significant hemolytic C4 activity after transplant of normal guinea pig bone marrow into lethally irradiated guinea pigs genetically deficient in C4. Each of five C4-deficient guinea pigs received 640 rads total body irradiation. They were immediately injected intracardially with 93 to 200 × 106 allogeneic nucleated marrow cells from Albany strain normal guinea pigs. The recipients were followed by sequential white cell counts and titrations of total complement, C1, C4, and C2. C4 activity, initially undetectable, was present as early as 24 days after transplantation and reached maximum levels by 45 to 60 days. C4 protein was also identified by using monospecific anti-guinea pig C4 serum. Amounts of C4 were sufficient to restore classical pathway function. C1 activity, initially 2 S.D. below normal, rose dramatically to normal or greater than normal levels. C2 activity also increased. These data demonstrate that allogeneic donor stem cells protected the lethally irradiated C4-deficient recipients and these allogeneic radiation chimeras subsequently synthesize circulating functional C4.