Glucocorticoids cause the regression of certain lymphoid tumours,
though the precise mechanism by which this is achieved is still not
fully understood. Consequently, I studied the action of a glucocorticoid, methylprednisolone (MPS), on human lymphoid cell lines as a
possible in vitro model for this effect.
MPS induced both a cytolethal and growth inhibitory response in
these cells, which I have defined on a kinetic and morphological basis.
The cytolethal response - measured by the ability of live cells
to exclude nigrosine after treatment over 48hr - was dose-dependent,
occurring around 10 MPS. Maximal lethal effects occurred only on
continuous exposure of the cells to MPS. Morphological changes, as
observed by light and electron microscopy, were consistent with
apoptosis followed by autolysis, with increased nigrosine uptake
correlating closely with onset of autolysis. A low background level
of apoptosis and autolysis was also present in control cultures.
The growth inhibitory response - measured by an increase in
population doubling time after treatment over several days - was dose-dependent, occurring within the concentration range 10 M -
10 Si MPS. Again, continuous exposure to MPS was necessary for the
response to be maintained. Morphological changes resulting from sub lethal damage were seen in mitochondria by electron microscopy; in
addition a small increase in the number of apoptotic and autolytic
cells was observed by light microscopy. Cell cycle kinetic analysis.revealed that growth inhibition was a stable effect caused by a
blockage of cells in G^ (or Gq); I was unable to determine whether
blocked cells were committed to death or maintained the ability to
return to cycle.
A correlation was made between my own results and biochemical
studies performed on human lymphoid cell lines by other workers in
our research group. The relationship between in vitro and in vivo
responses to glucocorticoids was also discussed
