Mitigation of lung injury after accidental exposure to radiation.
There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.
Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.
J
J
Mahmood
S
S
Jelveh
V
V
Calveley
A
A
Zaidi
S R
SR
Doctrow
R P
RP
Hill
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018788:Radioactive Hazard Release; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects / Q000528:radiation effects; D016019:Survival Analysis
D016207:Cytokines; D011837:Radiation-Protective Agents; D019833:Genistein