[Relationship between apoptosis of mouse thymic lymphocytes and expressions of bax, bcl-2 and bcl-XL after gamma-ray radiation with lethal dose].
OBJECTIVE
To observe the relationship between apoptosis of mouse thymic lymphocytes and the expressions of bax, bcl-2 and bcl-X(L) after gamma-ray radiation with lethal dose and provide the basis for treatment of acute severe radiation sickness.


METHODS
250 cleaning-grade C57 mice were randomly divided into 6 groups and treated with 0, 6, 9, 12, 15 and 20 Gy of whole body single gamma-irradiation, respectivety. The mice were killed by dislocation and then the thymus and peripheral blood samples were taken at 1-28 days and 3-12 months after irradiation. The lymphocytic apoptosis was analyzed by TUNEL. The expressions of bax, bcl-2 and bcl-X(L) were detected by in situ hybridization and immunohistochemical staining.


RESULTS
(1)Mouse peripheral leucocytes showed a transient elevation at 6 h after radiation and then decreased rapidly. The leucocyte's number reduced to minimal level at day 7 after 6 Gy gamma-irradiation and returned to basic normal value until one month after radiation. (2)24 h after irradiation the apoptotic rate of thymic lymphocytes increased swiftly, and apoptotic rate was positively correlated with radiation dose in the range of 6-12 Gy. There was no such a correlation after >/=15 Gy irradiation. (3)24 h after 6 Gy irradiation the apoptotic rate of thymic lymphocytes reached the maximal level. Afterwards it began to decrease, but still higher than that of control group even after 12 months. (4)3 h after 6 Gy radiation the expression of Bax protein in thymic lymphocytes increased immediately, and reached the highest value at 24 h. On the other hand, the expressions of Bcl-2 and Bcl-X(L) proteins reduced evidently at 3 h after radiation, reaching the lowest level at 24 h. Analysis of bax and bcl-2 mRNAs was concordant with the protein expression results.


CONCLUSIONS
After 6-12 Gy gamma-ray irradiation, the apoptotic rate of thymic lymphocytes is positively correlated with the radiation doses, suggesting that apoptosis is a major way of thymic lymphocyte death after </=12 Gy radiation. Increased Bax and decreased Bcl-X(L) expressions in lymphocyte suggest that both of them play an important role in thymic lymphocyte apoptosis caused by lethal dose radiation.
Cui
Yu-fang
YF
Department of Immunology, Institute of Radiation Medicine, AMMS, Beijing 100850, China. yufangc@vip.sina.com
Ding
Yan-qing
YQ
Xu
Han
H
Jiang
Zhu-jun
ZJ
Liu
Xiao-lan
XL
Dong
Bo
B
Mao
Jian-ping
JP
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D003037:Cobalt Radioisotopes; D005260:Female; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011829:Radiation Dosage; D011897:Random Allocation; D013950:Thymus Gland / Q000166:cytology / Q000528:radiation effects; D014916:Whole-Body Irradiation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics
D003037:Cobalt Radioisotopes; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein