Effects of low dose ionizing radiation on murine chronic granulomatous tissue.
OBJECTIVE
Substantial clinical evidence shows the efficacy of low-dose radiotherapy in the treatment of a wide variety of benign conditions. However, experimental investigations into these empirically clinical observations remain scarce. We investigated in vivo low-dose radiation effects on chronic granulomatous tissue by using the air pouch model in mice.


METHODS
Chronic granulomatous air pouches were induced in mice and dosed according to 4 protocols: group I: sham control; group II: 2 Gy on day 2; group III: 2 Gy on day 6; group IV: 5 daily doses of 0.5 Gy from day 2 to 6. On day 7 after granuloma induction the granuloma wet and dry weight was estimated, the vascular content was assessed by the formation of vascular casts incorporating carmine, the inducible nitric oxide synthase (iNOS)- and heme oxygenase 1 (HO-1)-expression in tissue homogenates was assessed by Western blot analysis, and the immunohistochemical localization of iNOS was carried out in cryostat sections of the granulomatous tissue.


RESULTS
We did not observe any significant reduction in granulomatous tissue wet weight or dry weight following the different radiation treatments, which indicates that anti-proliferative effects in response to the low radiation doses used, are probably not involved in the effects of anti-inflammatory radiotherapy. A single dose of 2 Gy on day 2, as well as fractionated treatment with 5 x 0.5 Gy lead to an increase in vascularity. iNOS-expression in the homogenized granulomatous tissue was decreased, being most pronounced after single-dose irradiation with 2 Gy on day 2, early on in the acute phase of inflammation. In contrast, the HO-1-expression was increased in all irradiated groups.


CONCLUSIONS
Low doses of radiation interfere with the NO- and the HO-1 pathway. Since NO contributes to several aspects of inflammation such as oedema formation and inflammatory pain, we put forward the hypothesis, that the inhibitory effect of low doses of ionizing radiation on the NO pathway is one radiobiological mechanism underlying the clinically observed efficacy of anti-inflammatory radiotherapy and might result in the reduction of swelling as well as relief of pain. Furthermore, the suppression of iNOS activity could be due to the increase in the stress protein HO-1 by low dose radiotherapy.
Hildebrandt
G
G
Klinik für Strahlentherapie und Radioonkologie, Universität Leipzig, Germany. hilg@server3.medizin.uni-leipzig.de
Seed
M P
MP
Freemantle
C N
CN
Alam
C A
CA
Colville-Nash
P R
PR
Trott
K R
KR
D000818:Animals; D015153:Blotting, Western; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism; D019047:Phantoms, Imaging; D011839:Radiation, Ionizing; D011879:Radiotherapy Dosage; D013997:Time Factors
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)