5-Fluorouracil-Induced Apoptosis in the Rat Thymus.
10.11637/kjpa.1999.12.1.139
- Author:
Keun Ja CHO
1
;
Soo Il KIM
;
Eun Jin YANG
;
Guo Dong ZHENG
;
Won Sik KIM
Author Information
1. Department of Anatomy, College of Medicine, Chungnam National University, Korea.
- Publication Type:Original Article
- Keywords:
5-Fluorouracil;
Thymus;
Apoptosis
- MeSH:
Animals;
Apoptosis*;
B-Lymphocytes;
Body Weight;
Cell Death;
Connective Tissue;
DNA;
Fibrosis;
Fluorouracil;
Germinal Center;
Glucocorticoids;
In Situ Nick-End Labeling;
Lymphocytes;
Models, Theoretical;
Radiation, Ionizing;
Rats*;
Rats, Sprague-Dawley;
Thymocytes;
Thymus Gland*
- From:Korean Journal of Physical Anthropology
1999;12(1):139-150
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Thymocyte death has been recognized as one of the best characterized experimental models of apoptosis that can be induced by a variety of stimuli such as glucocorticoids, ionizing radiation, anticancer drugs and toxins. The aim of this study was to investigate 5-fluorouracil (5-FU)-induced apoptosis in the rat thymus morphologically. Sprague Dawley rats were injected intramuscularly with 5-FU 100mg/kg body weight and 200mg/kg body weight, and were then sacrificed on day 1, 3, 6, 9 and 12 after treatment. H-E stain and the TUNEL method using the ApopTag kit were used. The results were as follows: 1. On day 1 and 3 after 5-FU treatment, thin cortex and prominent reduction of thymocytes in the cortex were detected. The degree of change was more extensive in the 5-FU 200 mg/kg-treated group than in the 5-FU 100 mg/kg-treated group. Pleomorphic apoptotic cells detected in the cortex were increased in the 5-FU 200mg/kgtreated group and on day 3 after treament. 2. In the 5-FU 100mg/kg-treated group, germinal centers appeared in the cortex on day 6 after treatment starting recovery. Formation of germinal centers continued to day 9 after treatment. In the germinal centers, there were large numbers of typical round apoptotic cells. The thymus exhibited normal architecture on day 12 after treatment. In the 5-FU 200 mg/kg-treated group, however, there were some that did not recover from involution of the thymus on day 6 after treatment and showed fibrosis with decrease of thymocytes and increase of connective tissue to day 9 after treatment. Others recovered and occurred similar changes to the 5-FU 100mg/kgtreated group. 3. 5-FU-induced pleomorphic apoptosis appeared mainly in the cortex and increased gradually depending on dose up to day 1, 3 after treatment. Apoptosis in the germinal centers first occurred from day 6 after treatment and revealed typical large round apoptotic cells. According to the above results, it is thought that 5-FU has an inhibitory effect on DNA synthesis, cell death and involution on surrounding tissue by direct action on thymocytes. The effect continues upto day 3~4 after treatment. Meanwhile, along with the recovery of the thymus from day 6 after treatment, new germinal centers appeared and active lymphocytes production occurred in the germinal centers, which was considered as compensatory reaction. To eliminate enormous B cells newly produced in the germinal center, active apoptosis would occur.
