Immunohistochemical proliferation markers may overestimate the growth potential after ionizing radiation: in vivo study in the rat anterior pituitary gland.
The effect of ionizing radiation on the expression of immunohistochemical proliferation markers was examined in the rat pituitary gland. Rats were irradiated in the pituitary region with a dose of 40 Gy, or were sham-irradiated as controls. Bromodeoxyuridine (BrdU) was given to the rats after one week, either one hour (Br-1 group) or 17 hours (Br-17 group) before perfusion fixation. Immunohistochemical staining for BrdU, topoisomerase II-alpha (TopoII), Ki-67 (MIB-5), p21WAF1/Cip1 (p21), and p27Kip1 (p27) was performed. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method. The mean BrdU labeling index (LI) and MIB-5 LI were significantly higher in the irradiated rats than in the sham rats in the Br-1 group. TopoII LI was higher in the irradiated rats than in the sham rats, although not significantly. p27-positive cells decreased in irradiated rats, but p21-positive cells increased more than in the sham rats. The number of apoptotic cells increased significantly after radiation. BrdU LIs were lower in the irradiated rats than in the sham rats in the Br-17 group. A few small BrdU-positive fragments with apoptotic features were phagocytosed in the anterior lobe cells. These results indicate that some "immunohistochemically proliferating cells" subsequently undergo apoptosis in the irradiated pituitary gland. The values of proliferative indices should be cautiously interpreted after irradiation of tissue.
Nakasu
Satoshi
S
Department of Neurosurgery, Shiga University of Medical Science, Ohtsu, Shiga. snakasu@belle.shiga-med.ac.jp
Nakasu
Yoko
Y
Fukami
Tadateru
T
Matsuda
Masayuki
M
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002455:Cell Division / Q000528:radiation effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D023421:Models, Animal; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II; D001973:Bromodeoxyuridine