A morphological study of the effect of chlorambucil during the S and G2
phases of the cell cycle of synchronized HEp-2 cancer cell populations
using computerized morphometry
Chlorambucil, a bisalkylating agent, used extensively in the treatment
of autoimmune and neoplastic diseases, is known to affect DNA synthesis.
However recent studies have revealed that it also affects the synthesis
of other nuclear protein constituents, especially histones. Since
histones play a major role in both the structural and functional
integrity of chromatin, we have analyzed the morphological effects of
this agent, using low dose conditions and synchronized populations of
HEp-2 cancer cells in the S and G2 phases of the cell cycle. Analyses at
the light and electron microscopy levels were undertaken using
synchronous image analysis techniques. Computerized morphometry was used
so as to evaluate various nuclear and cytological morphological
parameters. It was found that chlorambucil affects the organization of
chromatin, as well as other cellular parameters in a manner
characteristic of decreased tumor aggressiveness. A finding of
significance in this study was that chlorambucil exerted its influence
on all these morphological parameters only when treatment was initiated
at the beginning of the S phase and not during the second half of the S
phase or the G2 phase. (C) 2000 Elsevier Science Ltd. All rights
reserved
