Possible involvement of poly ADP-ribosylation in phenobarbital promotion of rat hepatocarcinogenesis.
The effects of inhibitors of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), luminol and 3-methoxybenzamide (MBA) on the rat liver tumor promotion activity of phenobarbital (PB) were assessed. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and placed on either basal diet, diet containing 0.05% PB, diet containing various doses of the inhibitors alone or diet containing 0.05% PB plus various doses of inhibitors for 10 weeks, and then killed. Quantitation of the development of glutathione S-transferase placental form-positive foci revealed that ABA at doses of 2 and 1.5, but not 1%, significantly inhibited the PB promotion activity. Luminol dose-dependently reduced PB promotion at doses of 3 and 6% but exerted no effects at the 1 and 2% levels. MBA also demonstrated a dose-dependent inhibitory influence at doses of 1 and 2%. The results are thus strongly suggestive of an involvement of poly ADP-ribosylation in the mechanisms underlying liver tumor promotion by PB.
Tsujiuchi
T
T
Department of Oncological Pathology, Nara Medical College, Japan.
Tsutsumi
M
M
Denda
A
A
Kondoh
S
S
Nakae
D
D
Maruyama
H
H
Konishi
Y
Y
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002273:Carcinogens; D004052:Diethylnitrosamine; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D008165:Luminol / Q000494:pharmacology*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D011916:Rats, Inbred F344
D001549:Benzamides; D002273:Carcinogens; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D004052:Diethylnitrosamine; D008165:Luminol; C025160:3-aminobenzamide; D005982:Glutathione Transferase; C025159:3-methoxybenzamide; D010634:Phenobarbital