Hepatocyte growth factor gene therapy prevents radiation-induced liver damage.
OBJECTIVE
To transfer human HGF gene into the liver of rats by direct electroporation as a means to prevent radiation-induced liver damage.


METHODS
Rat whole liver irradiation model was accomplished by intra-operative approach. HGF plasmid was injected into liver and transferred by electroporation using a pulse generator. Control rats (n = 8) received electrogene therapy (EGT) vehicle plasmid and another 8 rats received HGF-EGT 100 mug 48 h before WLIR. Expression of HGF in liver was examined by RT-PCR and ELISA methods. Apoptosis was determined by TUNEL assay. Histopathology was evaluated 10 wk after whole liver irradiation.


RESULTS
Marked decrease of apoptotic cells and down-regulation of transforming growth factor-beta 1 (TGF-beta1) mRNA were observed in the HGF-EGT group 2 d after liver irradiation compared to control animals. Less evidence of radiation-induced liver damage was observed morphologically in liver specimen 10 wk after liver irradiation and longer median survival time was observed from HGF-EGT group (14 wk) compared to control rats (5 wk). (P = 0.031).


CONCLUSIONS
For the first time it has been demonstrated that HGF-EGT would prevent liver from radiation-induced liver damage by preventing apoptosis and down-regulation of TGF-beta1.
Chi
Chau-Hua
CH
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Road, Shih-Lin, Taipei, Taiwan, China. m006565@ms.skh.org.tw
Liu
I-Li
IL
Lo
Wei-Yu
WY
Liaw
Bor-Song
BS
Wang
Yu-Shan
YS
Chi
Kwan-Hwa
KH
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015536:Down-Regulation; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008107:Liver Diseases / Q000517:prevention & control*; D011832:Radiation Injuries / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor