Background. A complete in vitro multi-stage carcinogenesis model for o
ral cancer was developed to examine chemopreventive strategies. In the
present study, the effects of EGCG [(-)-epigallocatechin-3-gallate],
the major constituent of green tea, is being examined to understand me
chanisms of action. Methods. Effects of EGCG on the cell populations w
ere examined with growth assays, cell cycle analysis, and western blot
s for retinoblastoma protein (pRB). Results. In each cell type, EGCG i
nhibited growth, with a decrease in efficacy as cells progressed from
normal to cancer. A G(1) block was induced with an increase in the und
erphosphorylated form of pRB; EGCG-induced inhibition was not permanen
t, cells recovered, and no resistance developed. Conclusions. Our mult
istage carcinogenesis model for chemoprevention was effective in defin
ing the chemopreventive value of EGCG. The observation that cancerous
oral epithelium was less responsive than normal or dysplastic tissues
has implication in the use of this agent, and the mechanisms responsib
le for this result remain to be defined. (C) 1998 John Wiley & Sons, I
nc.