We report here novel candidate chemopreventive agents active against experimental hepatocarcinogenesis. The
triazine derivatives 6-(2-chlorophenyl)-2,4-diamino-1,3,5-triazine (2CPDAT), 6-(3-chlorophenyl)-2,4-diamino-1,3,5-triazine (3CPDAT), 6-(4-chlorophenyl)-2,4-diamino-1,3,5-triazine (4CPDAT), 6-(4-pyridyl)-2,4-diamino-1,3,5-triazine (
PyDAT), and 6-(pyridine N-oxid-4-yl)-2,4-diamino-1,3,5-triazine (PyNODAT), synthesized in our laboratory, in addition to 6-(2,5-dichloro-phenyl)-2,4-diamino-1,3,5-triazine (
DCPDAT), or
irsogladine, which is a widely used anti-
ulcer drug, were investigated for potential chemopreventive effects in a rat liver medium-term bioassay system. A significant inhibitory influence on
enzyme-altered liver foci was found for 2CPDAT, 3CPDAT, 4CPDAT, and PyNODAT, but not for
DCPDAT or
PyDAT. The involvement of gap junctional intercellular communication in the inhibition was studied, but no change in gap junctional intercellular communication capacity in rat liver cells in vitro or in
gap junction protein (
connexin 32) expression in rat liver in vivo was noted. These results indicate that, although these
irsogladine analogues exert inhibitory effects on rat liver
carcinogenesis, their action is independent of modification of gap junctional intercellular communication.