Inhibition of methylazoxymethanol acetate initiation of colon carcinogenesis in rats by treatment with the poly(ADP-ribose)polymerase inhibitor 3-aminobenzamide.
To clarify the biological role of poly(ADP-ribose) in cancer induction in vivo, the influence of the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3-AB), on initiation of carcinogenesis in the colon and liver by a single application of methylazoxymethanol (MAM) acetate was investigated. Since 3-AB is rapidly metabolized and excreted in vivo when injected as a single dose, rats were given a continuous i.v. infusion of the compound (1200 mg/kg/day) for 4 days and injected with a single dose (35 mg/kg) of MAM acetate 4 h after the start of the experiment. Rats were killed 70 weeks after the beginning of the experiment. The incidence of colon tumors was significantly lower (t less than 0.025) in the 3-AB-treated group than in the carcinogen-only controls. Although significant numbers of glutathione S-transferase placental form positive foci were also induced in the liver of MAM-acetate-treated animals, 3-AB administration had no effect on their number and size. The results thus clearly demonstrated that continuous infusion of 3-AB during the initiation phase inhibited the development of MAM-acetate-induced colon tumors, but was not effective for the formation of preneoplastic foci in the liver.
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001391:Azo Compounds / Q000037:antagonists & inhibitors*; D001549:Benzamides / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced*; D005982:Glutathione Transferase / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000037:antagonists & inhibitors*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011230:Precancerous Conditions / Q000201:enzymology; D051381:Rats
D001391:Azo Compounds; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D008746:Methylazoxymethanol Acetate; C025160:3-aminobenzamide; D005982:Glutathione Transferase