Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap junctional intercellular communication.
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.
Hori
T
T
Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo.
Asamoto
M
M
Krutovskikh
V
V
Iwahori
Y
Y
Maeda
M
M
Toriyama-Baba
H
H
Takasuka
N
N
Tsuda
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D017630:Connexins / Q000032:analysis; D017629:Gap Junctions / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D000097002:Gap Junction beta-1 Protein
D016588:Anticarcinogenic Agents; D017630:Connexins; D005982:Glutathione Transferase; D014227:Triazines; D000097002:Gap Junction beta-1 Protein