Enhanced survival from radiation pneumonitis by combined irradiation to the skin.
OBJECTIVE
To develop mitigators for combined irradiation to the lung and skin.


METHODS
Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI); (2) 30 Gy soft X-rays to 10% area of the skin only; (3) 12.5 or 13 Gy WTI + 30 Gy skin irradiation after 3 hours; (4) 12.5 Gy WTI + skin irradiation and treated with captopril (160 mg/m(2)/day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI.


RESULTS
After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p < 0.0001). Collagen content was increased at 210 days after 13 Gy WTI vs. 13 Gy WTI + 30 Gy skin irradiation (p < 0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI + 30 Gy skin irradiation (p = 0.008).


CONCLUSIONS
Radiation to the skin given 3 h after WTI mitigated morbidity during pneumonitis in rats. Captopril enhanced the rate of healing of radiation-dermatitis after combined irradiations to the thorax and skin.
Department of Radiation Oncology.
Feng
F
Gao
Brian L
BL
Fish
Aniko
A
Szabo
Ashley
A
Schock
Jayashree
J
Narayanan
Elizabeth R
ER
Jacobs
John E
JE
Moulder
Zelmira
Z
Lazarova
Meetha
M
Medhora
D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D003094:Collagen / Q000737:chemistry; D005260:Female; D005355:Fibrosis; D008168:Lung / Q000528:radiation effects; D011832:Radiation Injuries; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000532:radiotherapy; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000532:radiotherapy*; D051381:Rats; D012867:Skin / Q000528:radiation effects*; D013909:Thorax / Q000528:radiation effects; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing; D014965:X-Rays
D003094:Collagen; D002216:Captopril
Combined radiation injuries; mitigation; nuclear accident; radiation to skin and lungs; radiological terrorism