The effect of BW12C on the radiosensitivity and necrosis of murine tissues and tumours.
BW12C is a drug that has the potential to induce normal tissue and tumour hypoxia by binding to haemoglobin, increasing its affinity for oxygen and thereby reducing oxygen availability to tissues. Initial results suggested that BW12C administration caused significant radioprotection of normal tissues and induced tumour necrosis, but variable results have been reported subsequently. This work was carried to extend the range of observations concerning the ability of BW12C to radioprotect normal tissues and tumours and to induce necrosis of tumours of the mouse. BW12C was administered as 70 mg/kg i.v. 15 min before irradiation of jejunum in CBA mice and of foot skin in WHT mice with single doses of 240 kVp X-rays while mice breathed gases of varying oxygen tensions. The radiosensitivities of these tissues were assessed by the crypt survival assay and the acute skin reaction, respectively. The radiosensitivity of CaNT tumours to single fraction irradiation was assessed by the regrowth delay assay following administration of single or multiple doses of BW12C at varying times to air-breathing CBA mice. The radiation response was compared to the radiosensitivity of clamped tumours. The effect of BW12C alone on tumours was assessed by regrowth delay and histological examination for necrosis. BW12C did not change the radiosensitivity of jejunal crypts irradiated while mice breathed air or 10% O2, or of foot skin when mice breathed 12% O2. BW12C protected foot skin by a factory of 1.1 when mice breathed air. Single or multiple doses of BW12C did not influence the radiosensitivity of CaNT tumours, although marked radioprotection could be induced by clamping the tumours during irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Stevens
G
G
Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney.
Hill
S A
SA
Joiner
M C
MC
Joiner
B
B
Johns
H
H
Williams
K
K
Denekamp
J
J
Nethersell
A B
AB
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007583:Jejunum / Q000528:radiation effects; D051379:Mice; D008808:Mice, Inbred CBA; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012867:Skin / Q000528:radiation effects
D001547:Benzaldehydes; D011837:Radiation-Protective Agents; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid