Antagonistic action of a tumor promoter and a poly(adenosine diphosphoribose) synthesis inhibitor in radiation-induced transformation in vitro.

Abstract

Transformation of mouse C3H 10T1/2 cells by X-irradiation in vitro was blocked by the addition of 1 mM 3-aminobenzamide, an inhibitor of polyadenosine diphosphoribose (poly[ADP-ribose]) synthesis immediately after irradiation. 3-Aminobenzamide also inhibited an increase in the frequency of transformants caused by the addition of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, 7 days after irradiation. These results demonstrate a role for poly(ADP-ribose) synthesis during the initiation and promotion stages of transformation. From previous studies it is known that poly(ADP-ribose) synthesis is stimulated by the DNA damage caused by X rays during initiation. During promotion, however, 12-O-tetradecanoylphorbol-13-acetate acted as a mitogen but did not induce detectable DNA damage, and we could detect no stimulation of poly(ADP-ribose) synthetase. The roles of poly(ADP-ribose) during initiation and during promotion must, therefore, be significantly different.

• Authors: C Borek, J E Cleaver
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 134 Issue 3 Pg. 1334-41 (Feb 13 1986) ISSN: 0006-291X [Print] United States
• PMID: 3947368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzamides
• Carcinogens
• DNA, Neoplasm
• Nucleoside Diphosphate Sugars
• Poly Adenosine Diphosphate Ribose
• 3-aminobenzamide
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Benzamides (pharmacology)
• Carcinogens (antagonists & inhibitors, pharmacology)
• Cell Transformation, Neoplastic (drug effects, radiation effects)
• Clone Cells
• DNA, Neoplasm (biosynthesis)
• Fibroblasts (radiation effects)
• Mice
• Mice, Inbred C3H
• Nucleoside Diphosphate Sugars (biosynthesis)
• Poly Adenosine Diphosphate Ribose (biosynthesis)
• Tetradecanoylphorbol Acetate (antagonists & inhibitors, pharmacology)