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Biomedical subjects

C W Song

Publications and source records attributed to C W Song.

At least 145 records · Page 8Linked to original sources

Uptake of carbon monoxide by C3H mice following X irradiation of lung only or total-body irradiation with 60Co.

Carbon monoxide uptake (Vco) and ventilation rate (VR) of C3H mice were determined at 14 weeks following either X irradiation of lungs only or total-body irradiation with 60Co at different dose rates. Following localized X irradiation of lung at 97 cGy/min there was a reduction in Vco, which was inversely related to radiation dose, with a small reduction below control levels being detected at 7 Gy, the lowest dose tested. An increase in VR could be detected only at doses of 11 Gy, or more. Another group of animals received 11.5 Gy total-body irradiation at either 26.2 or 4.85 cGy/min followed by transplantation with syngeneic bone marrow. Following total-body irradiation, Vco was significantly reduced by about 37% at the higher dose rate and 23% at the lower dose rate. In contrast, a trend toward elevated VR was detected only at the higher dose rate. The results indicate that Vco is a sensitive indicator of radiation-induced lung injury and that under the experimental conditions used Vco is a more sensitive indicator of radiation-induced lung injury in C3H mice than VR.

Animals↗

Effect of X irradiation and hyperthermia on vascular function in skin and muscle.

Vascular change by the combined treatments of radiation and hyperthermia was studied. The legs of rats were irradiated with 2000 rad of X rays in a single dose and heated at 43.0 degrees C for 1 hr at various times after irradiation, and the blood flow and vascular volume in the skin and muscle were determined with 125I-microspheres and 51Cr-RBC methods, respectively. Irradiation alone caused an immediate increase in blood flow and vascular volume in skin and muscle followed by a second increase during 2-4 weeks postirradiation. Heating also caused an immediate and profound increase in blood flow and vascular volume. When tissues were irradiated first and heated the increase in blood flow and vascular volume was generally greater than that caused by irradiation or heat alone for about 4 weeks postirradiation. The combined effects were either additive or more than additive depending on the interval between the irradiation and heating during this period. Hyperthermia at 40 days postirradiation increased the blood flow and vascular volume only slightly above that of the irradiated control, indicating that the combined effect of irradiation and hyperthermia became less than additive. It was concluded that the thermosensitivity of irradiated blood vessels in skin and muscle for 3-4 weeks postirradiation was at least similar or greater than that of unirradiated controls. The thermosensitivity of vessels appeared to decline 40 days after irradiation.

Animals↗

Effect of hyperthermia on hypoxic cell fraction in tumor.

The effect of hyperthermia on the proportion of hypoxic cells in SCK mammary tumor of A/J mice was investigated. About 45% of clonogenic cells in the unheated control tumor were radiobiologically hypoxic. Upon heating with a 43.5 degree C water bath for 30 min, the proportion of hypoxic cells increased and then decreased: it was 95% at 5 hr and 60% at 12 and 24 hr after heating. Despite the increase in the proportion of hypoxic cells 5 hr after heating, the absolute number of hypoxic cells in the tumors at this time was significantly smaller than that in the unheated control tumors because of a decrease in the total number of surviving tumor cells. The initial increase in the proportion of hypoxic cells after heating may be attributed mainly to vascular occlusion. Proliferation of cells in the oxic area, and thus an increase in oxic cell number, appears to account for the decline in the proportion of hypoxic cells from 5 hr after heating.

Animals↗

Changes in thermosensitivity of mouse mammary carcinoma following hyperthermia in vivo.

The time course of change in thermosensitivity of SCK tumor cells in vivo was investigated following preheating at 43.5 degrees for 30 min. At varying times after the preheating with water bath, tumors were subjected to graded doses of second heating at 43.5 degrees in vivo, and cell survival was determined by using in vitro cloning method. Thermosensitivity of the tumor cells in vivo [duration of heating for exponential inactivation of cells to 1/e (Do): 15.5 min] gradually increased after the preheating, reaching a maximum increase at 5 hr (Do: 7.5 min), and then decreased thereafter, due probably to a development of thermotolerance. Maximum thermotolerance was observed at 12 hr after the preheating, leading to a 3-fold increase in Do (48 min). The thermotolerance gradually decayed for several days thereafter. The initial increase in thermosensitivity might be attributed to the acidic and nutritionally deprived intratumor environment as a result of vascular damage in heated tumor. It appears that thermotolerance gradually develops as time elapses and that it eventually overcomes the thermal sensitization of tumor cells in vivo.

Animals↗

Physiological factors in hyperthermia.

The blood flow in normal tissues, i.e., skin and muscle, increases remarkably when heated at temperatures commonly used in hyperthermia (42 degrees -45 degrees C), whereas that in tumor appears to increase slightly when heated at temperatures below 41 degrees -42 degrees C but drastically decreases at temperatures above 42 degrees C. Histopathological studies of the heated tumors demonstrated a pronounced hyperemia, vascular occlusion, and hemorrhage. Due to the vascular occlusion, the dissipation of heat in the tumors becomes inefficient, and the temperatures in the tumor rise higher than those in normal tissues during hyperthermia at temperatures above 42 degrees C. The pH in tumors significantly decreases upon heating. The acidic conditions in the tumors enhances the thermal killing of tumor cells and inhibits the repair of thermal damage and development of tolerance to heat. The mechanism of the decrease in blood flow and pH in the heated tumors is not clear, but these two phenomena seem closely related. The preferential effect of hyperthermia on tumors may be attributed to the higher temperature relative to normal tissue temperature during heating and also to the decrease in the pH upon heating.

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Effect of x-irradiation on immunocompetency of T-lymphocytes.

Effect of x-irradiation on various aspects of cell-mediated immune reactions is studied. The irradiated splenic lymphocytes could transform to blast cells upon stimulation with PHA, but could not divide into small lymphocytes. It was concluded that irradiation at doses higher than 500 rads inhibits the differentiation of lymphocytes to effector cells upon stimulation with antigens. The irradiated immune lymphocytes were able to kill target tumor cells when the cytotoxicity was tested immediately after irradiation with doses as high as 500 rads. The cytotoxicity of immune lymphocytes diminished, however, 7--10 hours after irradiation. The splenic lymphocytes irradiated with doses as high as 200 rads could stimulate allogeneic lymphocytes 2 days after the irradiation. It thus appeared that irradiation cannot immediately abolish the antigenicity of lymphocytes to stimulate allogeneic lymphocytes. The combined effect of irradiation and T-cell-mediated immune reaction to reduce clonogenecity of target tumor cells in vitro is simple additive.

Autoradiography↗

The effect of hyperthermia on vascular function, pH, and cell survival.

Blood flow in rat skin and muscle increased three- to fourfold during heating at 43 degrees C for one hour, while that in Walker tumors did not change significantly; however, blood flow in the tumors decreased a few hours after heating at 45 degrees C. The temperature of Walker tumors was significantly higher than in the muscle during heating, probably due to inefficient heat dissipation caused by the sluggish blood flow. Severe vascular occlusion occurred in SCK tumors in mice after heating at 41.5-45.0 degrees C. Upon heating, the pH in the tumors significantly decreased, while that in the muscle increased. The clonogenic cell number continuously decreased when SCK tumors were left in situ after hyperthermia. The vascular occlusion and increase in acidity may account for the progressive death of tumor cells after heating.

Animals↗

Blood flow in normal tissues and tumors during hyperthermia.

The effect of hyperthermia on the blood flow was studied in skin, muscle, and Walker 256 carcinoma implanted in the legs of SD rats. The radioactive microsphere method was used to measure the blood flow. Hyperthermia for 1 hour with water at 43 degrees C increased the blood flow in skin and muscle by about threefold to fourfold. On the contrary, hyperthermia had no appreciable effect on the blood flow in tumors. Consequently, during hyperthermia blood flow in the skin and muscle surrounding the tumors was greater than that in tumors larger than about 2 g. Despite the apparent increase in heat dissipation by the increased blood flow, the temperature of the skin was 42.6-42.8 degrees C, and the temperature at the core of tumors larger than 2 cm in diameter was 42.3-42.7 degrees C during the hyperthermia. The lower temperature in the muscle could be attributed to an increase in heat dissipation as a result of the increased blood flow. This differential rise in temperature by heating may account in part for the differential effect of hyperthermia on tumors and normal tissues in vivo.

Animals↗

Role of vascular function in response of tumors in vivo to hyperthermia.

The response of SCK tumor cells in vivo and in vitro to heat was compared, and the relationship between the kinetics of cell death and vascular function in tumors in vivo after hyperthermia was studied. The number of clonogenic cells in tumors excised immediately after heating was significantly less than that in the in vitro culture treated with the same heat doses. This suggested that the tumor cells in vivo are far more sensitive to direct damage by heat than are the cells in vitro. When the tumors were left in situ after hyperthermia at 43.5 degrees for 30 min, there was a progressive decrease in cell survival until 6 to 12 hr after the heating. The study of intravascular volume using the 51Cr-labeled red blood cell method indicated that severe vascular occlusion occurs in the tumor after hyperthermia. It therefore appeared that delayed cell death in tumors in vivo after hyperthermia resulted from an insufficient supply of oxygen and nutrients and an increase in acidity due to the vascular occlusion. Both the direct damage to tumor cells and the indirect damage to tumor cells as a consequence of vascular occlusion may play important roles in the eradication of tumors by hyperthermia.

Animals↗

5-Thio-D-glucose selectively potentiates hyperthermic killing of hypoxic tumor cells.

To investigate the mechanisms by which heat affects cancer cells, we used 5-thio-D-glucose, an inhibitor of glycolysis in HeLa S-3 cells, under aerobic and hypoxic conditions at temperatures ranging from 37 degrees to 43 degrees C. Drug alone or heat alone killed a minimum number of cells under aerobic or hypoxic conditions. Exposure to drug and hyperthermia selectively increased the number of cells killed under hypoxic conditions at temperatures as low as 40.5 degrees C but had little effect on cells incubated under aerobic conditions. These results suggest that the glycolytic pathways is a primary site of hyperthermic damage leading to cell death.

Aerobiosis↗

Effect of hyperthermia on vascular functions of normal tissues and experimental tumors; brief communication.

The effect of hyperthermia on vascular volume and vascular permeability of the Walker carcinoma 256, skin, and muscle of inbred SD male rats was investigated. Whereas heating at 43 degrees C for 1 hour induced a significant increase in the functional vascular volume and vascular permeability in the skin and muscle, it did not change these vascular functions in the tumors. The increased vascular volume in the normal tissues suggested an increased circulation, which may enhance the dissipation of heat and result in a differential effect of hyperthermia on normal tissues and tumors.

Animals↗

Effects of combined radiotherapy and immunotherapy with the use of pyran copolymer on murine fibrosarcoma.

A weakly immunogenic, 3-methylcholanthrene-induced, subcutaneous fibrosarcoma syngeneic to inbred C3H/HeJ mice was used. Pyran copolymer was injected either directly into the tumor, ip, or iv as soon as tumors appeared or when tumors were 8 mm in diameter. One, three, or five doses of pyran copolymer at 10 or 20 mg/kg/dose were injected, with multiple doses being given every other day. Pyran copolymer injected intratumorally once, three times, or five times significantly retarded tumor growth and prolonged the survival times of the hosts. Of the other routes and doses, only pyran copolymer given three times iv significantly retarded tumor growth, but none of these significantly prolonged the survival times of the hosts. Pyran copolymer alone did not induce any complete regression of tumor. Local tumor irradiation with a single exposure to 2,000 rads of X-ray induced complete regressions in some mice, but a higher percentage of tumor cure was observed when tumor irradiation was followed by pyran copolymer treatment.

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