Differences in ICAM-1 and TNF-alpha expression between large single fraction and fractionated irradiation in mouse brain.
OBJECTIVE
To elucidate the brain molecular response to irradiation. The expression of the intercellular adhesion molecule (ICAM-1) and tumour necrosis factor-alpha (TNF-alpha) in the mouse brain was compared after single-dose and fractionated whole-brain irradiation.


METHODS
Mice received a single dose of 2, 10 or 20 Gy or a fractionated dose (2 Gy day(-1)) of 10, 20 or 40 Gy. ICAM-1, and TNF-alpha mRNA expression were quantified by the highly sensitive real-time polymerase chain reaction technique. Expression of ICAM-1 protein was quantified by dual-labelled monoclonal antibody assay.


RESULTS
After a 20-Gy single dose, there was an increase in ICAM-1 and TNF-alpha mRNA levels (14- and 11-fold, respectively) as well as a significant increase in the level of ICAM-1 protein (p=0.0243). The expression of ICAM-1 and TNF-alpha mRNA increased at the end of the 40-Gy fractionated regimen (3.55- and 2.30-fold, respectively).


CONCLUSIONS
The molecular response of the brain to single-dose irradiation was rapid, while its response to fractionated irradiation was slow. This finding is consistent with clinical observations and could be of use when designing strategies to mitigate radiation sequelae.
Gaber
M W
MW
Department of Radiation Oncology, St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794, USA. waleed.gaber@stjude.org
Sabek
O M
OM
Fukatsu
K
K
Wilcox
H G
HG
Kiani
M F
MF
Merchant
T E
TE
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1