Radiation hepatology of the rat: the effects of the proliferation stimulus induced by subtotal hepatectomy.
The effect of an 80 to 90% hepatectomy in stimulating proliferation immediately after irradiation of the liver was studied. A dose of 15 Gy was not lethal for animals with intact livers, but all animals with subtotal hepatectomies exposed to this dose died from apparent liver failure 28 to 60 days after exposure. To elucidate the mechanism for this mortality, plasma aspartate aminotransferase, retention of intravenous injected rose bengal, liver weight and liver hydroxyproline content were measured 0 to 90 days after 15 Gy irradiation of the liver to determine temporal changes in necrosis, function, mass and fibrosis, respectively, in animals with either intact livers or livers with subtotal resection. Irradiation of the liver had no significant effect on these parameters in animals with intact livers. In subtotally hepatectomized animals the same radiation dose that suppressed liver mass restoration significantly increased hepatocyte necrosis within 7 days, which was followed by increased liver hydroxyproline concentration and hepatic dysfunction. This radiation-induced temporal change in hepatic dysfunction correlated with increased concentration of hydroxyproline but not with liver mass, indicating that liver fibrosis was the cause of hepatic dysfunction. Since similar sequelae are produced in intact livers after higher doses and longer intervals after irradiation, the proliferation stimulus induced by partial hepatectomy must accelerate the expression of damage and lower the radiation tolerance of the liver. However, in subtotally hepatectomized animals radiation-induced hepatocyte necrosis precedes fibrosis, whereas the reverse is normally true for animals with intact livers.
Geraci
J P
JP
Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Mariano
M S
MS
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002455:Cell Division; D004307:Dose-Response Relationship, Radiation; D006498:Hepatectomy; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000473:pathology / Q000528:radiation effects*; D008115:Liver Regeneration; D008297:Male; D009336:Necrosis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016212:Transforming Growth Factor beta; D001219:Aspartate Aminotransferases; D006909:Hydroxyproline