Modification of the radiation response of pig skin by manipulation of tissue oxygen tension using anesthetics and administration of BW12C.
The importance of tissue oxygen tension on radiosensitivity was studied by examining modifications in the incidence of moist desquamation in pig skin after irradiation with strontium-90 plaques. The effects were analyzed using quantal dose-response data and comparisons were made using ED50 values for moist desquamation. Under standard anesthetic conditions of 2% halothane, approximately 70% oxygen, and approximately 30% nitrous oxide, the ED50 value (+/- SE) for moist desquamation was 27.32 +/- 0.52 Gy with no significant variation in radiosensitivity between dorsal, lateral, and ventral skin sites on the flank. Irradiation with 2% halothane and air increased the ED50 to 31.25 +/- 0.94 Gy, primarily due to an increased radioresistance of the dorsal sites. When combined with BW12C, a drug which binds oxygen selectively to hemoglobin and hence reduced the oxygen availability to tissues, a further increase in the ED50 values was observed. This was approximately 39 Gy with BW12C concentrations of 30 mg/kg and 50 mg/kg b.w. of BW12C, indicating a dose modification factor (DMF) of approximately 1.26. However, when animals were breathing the standard gas mixture, this DMF was reduced to 1.15 for 30 mg/kg of BW12C, indicating that a higher level of oxygen partly counteracted the effects of the drug in these studies with BW12C. The greatest variability in radiosensitivity was seen in the dorsal fields. This suggested complex physiological adaptation, a phenomenon that might also explain the absence of any modification of the radiation response when 100 mg/kg of BW12C was used.
van den Aardweg
G J
GJ
CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), Churchill Hospital, U.K.
Hopewell
J W
JW
Barnes
D W
DW
Sansom
J M
JM
Nethersell
A B
AB
D000447:Aldehydes / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D000818:Animals; D001547:Benzaldehydes; D006221:Halothane; D009609:Nitrous Oxide; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D011836:Radiation Tolerance; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013552:Swine
D000447:Aldehydes; D001547:Benzaldehydes; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; D009609:Nitrous Oxide; D010100:Oxygen; D006221:Halothane