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 livertumor 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 containing0.05% PB, diet containing various doses of the inhibitors aloneor diet containing 0.05% PB plus various doses of inhibitorsfor 10 weeks, and then killed. Quantitation of the developmentof glutathione S-transferase placental form-positive foci revealedthat ABA at doses of 2 and 1.5, but not 1%, significantly inhibitedthe PB promotion activity. Luminol dose-dependently reducedPB promotion at doses of 3 and 6% but exerted no effects atthe 1 and 2% levels. MBA also demonstrated a dose-dependentinhibitory influence at doses of 1 and 2%. The results are thusstrongly suggestive of an involvement of poly ADP-ribosylationin the mechanisms underlying liver tumor promotion by PB.