• Radiation Oncology Journal
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• v.9 no.1
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• pp.7-15
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• 1991

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.1-6
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• 1990

In the present study, a perfluorchemical emulsion (Fluosol-DA $20\%$) did not alter $D_o\;and\;D_q$ values on cell survival curve, indicating that the lack of a direct effect of Fluosol-DA $20\%$ on cellular radiosensitivity in vitro. The effect of Fluosol-DA $20\%$ injection in combination with carbogen breathing was determined on the hypoxic cell fraction in SCK tumors. The hypoxic cell fraction in control SCK tumors was 0.39. This value decreased to 0.05 when the mice were i.v. injected with 12 ml/kg of Fluosol-DA $20\%$ in a carbogen atomosphere. The measured mean and median $PO_2$ values with a microelectrode in the control tumors was 9 mmHg and 4 mmHg, respectively. The treatment of the SCK tumors in the host mice with injected Fluosol-DA $20\%$ in combination with carbogen breathing increased the mean and median $PO_2$ values to 67 mmHg and 62 mmHg, respectively. Using carbogen breathing alone caused a moderate increase of tumor $PO_2$. But Fluosol-DA $20\%$ injection alone caused little change $PO_2$ in the tumor. It was concluded that the combination of Fluosol-DA injection and carbogen breathing is an effective means to improve oxygenation of tumors.