Protection of pig epidermis against radiation-induced damage by the infusion of BW12C.
BW12C, which was developed as an agent for the treatment of sickle cell anaemia, increases the binding of oxygen to haemoglobin and hence reduces the availability of oxygen to tissues. Due to these changes in oxygen availability BW12C could act as a protector against radiation-induced injury to normal tissues. In this study the potential value of BW12C, as a radioprotector, was studied in the irradiated epidermis of the pig. The infusion of BW12C caused an instant left shift of the oxygen dissociation curve, an effect that lasted for approximately 1.5 h. This left shift in the oxygen dissociation curves increased with increasing dose of the drug. There appeared to be no long-term systemic effects produced by doses of 20-100 mg/kg of BW12C. In the first 90 min after the infusion of BW12C skin fields were irradiated with single doses of beta-rays from strontium-90 plaques. The incidence of moist desquamation was used as an endpoint for assessing the severity of the radiation response. With animals breathing approximately 70% oxygen in the anaesthetic gas mixture, the ED50 values for moist desquamation were 30-31 Gy after a dose of 30 and 50 mg/kg, and 37-38 Gy for 75 and 100 mg/kg doses of BW12C. These ED50 values were significantly higher than the value of 27.3 Gy for radiation alone. This indicated dose modification factors (DMF) with mean values of approximately 1.13 and approximately 1.40 for irradiation following the infusion of low (30-50 mg/kg) and high (75-100 mg/kg) doses of the drug, respectively. With the animals breathing air (approximately 21% of oxygen) in the 2% halothane anaesthesia gas mixture, irradiation in the presence of 30 and 50 mg/kg of BW12C resulted in ED50 values of approximately 39 Gy for moist desquamation, which was significantly higher than the value of 31.2 Gy for radiation alone. Surprisingly, a higher dose of 75 mg/kg of BW12C resulted in a lower ED50 value for moist desquamation of 34.38 Gy. Irradiation in the presence of a dose of 100 mg/kg of BW12C produced an ED50 value which was not significantly different from that for radiation alone. In the situation where animals were breathing air (approximately 21% oxygen) during irradiation a DMF of 1.14 was obtained for irradiation alone, when the results were compared with those for irradiation alone with approximately 70% oxygen in the anaesthetic gas mixture.(ABSTRACT TRUNCATED AT 400 WORDS)
CRC Normal Tissue Radiobiology Research Group, Research Institute (University of Oxford), Churchill Hospital, Headington, UK.
G J
GJ
van den Aardweg
J W
JW
Hopewell
G E
GE
Adams
D W
DW
Barnes
J M
JM
Sansom
I J
IJ
Stratford
A B
AB
Nethersell
D000818:Animals; D001547:Benzaldehydes / Q000008:administration & dosage*; D001610:Beta Particles; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D007262:Infusions, Intravenous; D010100:Oxygen / Q000008:administration & dosage; D010108:Oxyhemoglobins / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011855:Radiodermatitis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D012039:Regional Blood Flow / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000098:blood supply; D013326:Strontium Radioisotopes; D013552:Swine
D001547:Benzaldehydes; D010108:Oxyhemoglobins; D011837:Radiation-Protective Agents; D013326:Strontium Radioisotopes; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; D010100:Oxygen