A STUDY OF CELL KINETICS 
IN THE RAT THYMUS AFTER 
PERTURBATION BY DEXAMETHASONE 
J, C. Pierce* 
Cell kinetics were studied in the normal rat thymus 
and after the intravenous injection of 0.2 mg. of dexa- 
methasone. This caused a decrease in DNA-P content 
from 910 jugm to 88 figm. 3 days after injection with a 
return to 798 /igm at 10 days. The hourly fractional 
rate of DNA turnover estimated from the time specific 
activity curves of DNA-P and acid soluble phosphorus 
after the intraperitoneal injection of decreased 
from a control level of 0.040/hr. to a minimum of 
0.004/hr., 24 hours after dexamethasone. Cell produc- 
tion in the thymus was reduced from 54 x lOVhr. in 
the normal thymus to 1.8 x 10° at 24 hours after dexa- 
methasone and returned to normal at 10 days. Endo- 
genous cell production was more than sufficient to account 
for the observed increment in DNA-P during regenera- 
tion of the thymus. 
The data suggest that cells are produced by a stem 
cell population which constitutes 20% of the thymus 
and which divides repeatedly with a turnover time of 
approximately 5 hours. One-half of the daughter cells 
are retained within the stem cell population. Of the re- 
maining newly formed cells, approximately three quar- 
ters are probably destroyed in the thymus soon after 
mitosis is completed. The remaining cells enter the small 
thymocyte compartment where diiferentiation occurs. It 
was estimated that these cells are retained for 48-72 
hours before they are lost from the thymus to second- 
ary lymphoid organs; The rate of loss of DNA from the 
thymus and the profound decrease in the rate of cell 
production which followed a single dose of dexametha- 
sone suggested that all of the cells in the replicating 
compartment and 20% of the cells in the small thymo- 
cyte compartment were exquisitely sensitive to killing 
by dexamethasone, but with the passage of time after 
mitosis, the small thymocytes differentiated and lost this 
sensitivity. 
INTRODUCTION 
The thymectomy experiments of Good and 
co-workers^ in neonatal animals have indicated 
the central role which the thymus plays in the 
development of immunological capacity. The ex- 
periments of Metcalf and his co-workers have 
* Health Sciences Division, Virginia Commonwealth University, 
Richmond, Virginia. 
suggested that the thymus in the adult contin- 
ues to produce very large numbers of cells,^'* 
and that the presence of the thymus still plays 
an important role in sustaining the immunologi- 
cal capacity of the animal.^ The present experi- 
ments were undertaken to study the kinetics of 
thymus cell production and loss from the adult 
thymus during the major changes in the rate of 
cell production caused by dexamethasone which 
is a synthetic adrenal corticosteroid with great 
anti-inflammatory potency and no sodium re- 
taining effect. 
METHODS 
Adult female Sprague-Dawley rats which 
weighed approximately 200 gms. were used. 
The rats were obtained from Charles River and 
acclimated in an air conditioned room for at 
least one week prior to the first experimental 
manipulation. Dexamethasone (9 a-fluoro-lG 
a-methyl-prednisolone) was given as a single 
dose of 0.2 mg. intravenously via a tail vein at 
various intervals prior to sacrifice. The deoxyri- 
bonucleic acid (DNA) content of the thymus 
was estimated by the diphenylamine method of 
Burton.^ DNA was used as a standard and re- 
sults are reported as DNA phosphorus (DNA- 
P). The hourly fractional turnover rate for 
DNA was estimated from the time specific ac- 
tivity curves of phosphorus in DNA and in the 
acid soluble phosphorus pool at one and two 
hours after the intraperitoneal injection of one 
fj.c of ^-P per gram body weight as has been pre- 
viously described." The rate of cell production 
was calculated by multiplying the DNA-P con- 
tent of the thymus times the DNA hourly turn- 
over rate and dividing by the average DNA-P 
content of a rat cell, 0.678 x lO"^^ gms.^ 
755 
