Effects of genistein following fractionated lung irradiation in mice.
OBJECTIVE
This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response.


METHODS
C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet ( approximately 10mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma).


RESULTS
Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed.


CONCLUSIONS
Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.
Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ont., Canada.
Andrea E
AE
Para
Andrea
A
Bezjak
Ivan W T
IW
Yeung
Jake
J
Van Dyk
Richard P
RP
Hill
D000818:Animals; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D019833:Genistein / Q000494:pharmacology*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests; D009374:Neoplasms, Experimental; D011336:Probability; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000401:mortality / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental; D011836:Radiation Tolerance / Q000187:drug effects; D011839:Radiation, Ionizing; D011897:Random Allocation; D012016:Reference Values; D015996:Survival Rate
D016207:Cytokines; D019833:Genistein