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© 1990 Oxford University Press

other

Possible involvement of poly ADP-ribosylation in phenobarbital promotion of rat hepatocarcinogenesis

Toshifumi Tsujiuchi, Masahiro Tsutsumi, Ayumi Denda, Satoshi Kondoh, Dai Nakae, Hiroshi Maruyama and Yoichi Konishi 1

Department of Oncological Pathology, Cancer Center, Nara Medical College 840 Shijo-cho, Kashihara, Nara 634, Japan

1To whom reprint requests should be sent

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.


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