Transforming growth factor-beta 1 expression in irradiated liver.
The expression of transforming growth factor-beta 1 (TGF-beta 1) in the liver of irradiated rats was increased in a dose-dependent fashion 9 months after irradiation. Expression of TGF-beta 1 was confined primarily to hepatocytes in the pericentral region of the liver, and the percentage of hepatocytes strongly positive for TGF-beta 1 was significantly correlated with the extent of fibrosis. We further showed that a localized injection of TGF-beta 1 into normal rat liver elicited a strong fibrotic reaction at the injection site. These results suggest that the increased hepatic concentration of TGF-beta 1 in response to radiation injury may be important in the pathogenesis of radiation hepatitis. TGF-beta 1 was also found to be present at a significantly higher concentration in unirradiated human hepatocytes than in normal rat hepatocytes, implying that the propensity for humans to develop radiation hepatitis may result in part from the elevated levels of TGF-beta 1 normally found in human liver.
Anscher
M S
MS
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710.
Crocker
I R
IR
Jirtle
R L
RL
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006505:Hepatitis / Q000209:etiology; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D011832:Radiation Injuries / Q000209:etiology; D011836:Radiation Tolerance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015291:Transforming Growth Factors / Q000378:metabolism*
D015291:Transforming Growth Factors; D006909:Hydroxyproline