Suppressive effect of irsogladine maleate on diethylnitrosamine-initiated and phenobarbital-promoted hepatocarcinogenesis in male F344 rats.
Modifying effects of irsogladine maleate (IRG) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis were examined in male F344 rats. Six-week-old rats were divided into 8 groups. Groups 1 through 4 were given a single i.p. injection of DEN (200 mg/kg body weight) at the start of the experiment, whereas groups 5 through 8 received a single i.p. injection of saline as the vehicle treatment. Groups 1 and 8 were kept on the basal diet and distilled water throughout the experiment (36 weeks). Groups 2 and 7 were exposed to 500 ppm phenobarbital (PB) in the drinking water, starting one week after the carcinogen or vehicle treatment. Groups 3 and 5 were fed the diet mixed with 125 ppm IRG from one week after DEN or vehicle treatment. Groups 4 and 6 were given 125 ppm IRG-containing diet and drinking water with 500 ppm PB after the carcinogen or vehicle treatment. Liver neoplasms developed in groups 1 (1/15 rats, 7%) and 2 (14/14 rats, 100%). However, no liver tumors were found in rats of groups 3 through 8. Incidence and average number of liver neoplasms in group 4 (0/14 rats, 0%) were less than those in group 2 (P < 0.0001). The number of glutathione S-transferase placental form (GST-P)-positive liver cell foci in group 3 or 4 was significantly smaller than that in the appropriate control (P < 0.01, P < 0.001, respectively). The average and unit areas of these foci in group 4 were also significantly smaller than those in group 2 (P < 0.001, P < 0.05, respectively). These results suggest that IRG could be a chemopreventive agent for rat liver carcinogenesis.
Sugie
S
S
Department of Pathology, Gifu University School of Medicine.
Okamoto
K
K
Ueda
F
F
Watanabe
T
T
Tanaka
T
T
Mori
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000032:analysis; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000737:chemistry / Q000517:prevention & control*; D008297:Male; D010634:Phenobarbital; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014227:Triazines; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; C041836:irsogladine; D010634:Phenobarbital