Inhibitory effect of chlorophyllin on diethylnitrosamine and phenobarbital-induced hepatocarcinogenesis in male F344 rats.
Modifying effects of chlorophyllin (CHL) on the diethylnitrosamine (DEN)-phenobarbital (PB) hepatocarcinogenesis model were examined in rats. Five-week-old male F344 rats were divided into 8 groups. Groups 1 through 5 were given i.p. injections of DEN (100 mg/kg body weight) once a week for 3 weeks beginning one week after the start of the experiment, while groups 6 through 8 received vehicle treatment. Groups 1, 2, 3 and 7 received drinking water with 500 ppm PB from one week after the end of carcinogen or vehicle treatment. CHL-containing diet (2000 ppm) was given to group 2 during the initiation phase and to groups 3 and 5 during the promotion and the post-initiation phase, respectively. Group 6 was given the experimental diet alone throughout the experiment (24 weeks). Liver neoplasms were present in DEN-treated groups and PB treatment promoted liver tumorigenesis. The incidences of adenoma in groups 2 and 3 were significantly smaller than in group 1 (P<0.05 and P<0.02), although the reductions in the incidences of liver cell cancer were not significant. The average numbers of liver neoplasms/rat in group 2 were significantly smaller than in group 1 (P<0.05-P<0.005). Glutathione S-transferase placental form-positive foci were also significantly decreased by CHL treatment (P<0.05 and P<0.001). DEN and PB exposure increased liver ornithine decarboxylase activity and this increase was significantly inhibited by feeding of CHL during the initiation phase (P<0.001). These results suggest that CHL is a chemopreventive agent for liver neoplasia.
Sugie
S
S
Institute of Laboratory Animals, Gifu University School of Medicine, Japan.
Okamoto
K
K
Makita
H
H
Ohnishi
M
M
Kawamori
T
T
Watanabe
T
T
Tanaka
T
T
Mori
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D002735:Chlorophyllides / Q000494:pharmacology*; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D009955:Ornithine Decarboxylase / Q000032:analysis; D010634:Phenobarbital; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D002273:Carcinogens; D002735:Chlorophyllides; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D009955:Ornithine Decarboxylase; C007020:chlorophyllin; D010634:Phenobarbital