Pi-class glutathione-S-transferase-positive hepatocytes in aging B6C3F1 mice undergo apoptosis induced by dietary restriction.
Liver sections from aging ad libitum-fed and diet-restricted B6C3F1 male mice were evaluated immunohistochemically for pi-class glutathione S-transferase (GST-II). GST-II immunostaining of hepatocytes was diffuse and occurred in periportal regions of hepatic acinus, whereas perivenous areas were weakly stained or were stain-free. Expression of GST-II was significantly diminished in diet-restricted mice in all age groups and was associated with a marked decrease in liver tumor development. As most spontaneous liver tumors were GST-II positive, it can be speculated that they developed from GST-II positive initiated hepatocytes. To determine whether dietary restriction induces apoptosis in GST-II-positive hepatocytes, 24-month-old ad libitum-fed mice were introduced to 40% diet restriction. After 1 week of diet restriction, a decrease in GST-II expression was associated with a threefold increase in the frequency of apoptotic bodies as detected by terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling of DNA fragments. A two-step immunohistochemical procedure revealed that approximately 70% of apoptotic bodies were GST-II positive. These results suggest that spontaneous, potentially preneoplastic hepatocytes in tumor-prone B6C3F1 mice are eliminated by apoptosis with dietary restriction.
Division of Nutritional Toxicology, FDA-National Center for Toxicological Research, Jefferson, Arkansas, USA.
L
L
Muskhelishvili
A
A
Turturro
R W
RW
Hart
S J
SJ
James
D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005260:Female; D005508:Food Deprivation; D005982:Glutathione Transferase / Q000032:analysis* / Q000145:classification; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D005982:Glutathione Transferase