title: Potentiation of sister chromatid exchange by 3-aminobenzamide is not modulated by topoisomerases or proteases.
abstract: Poly(ADP-ribose) is synthesized in response to DNA strand breaks and covalently modifies numerous intracellular proteins. We have proposed that this modification regulates, i.e., inhibits, the activity of these enzymes, e.g., topoisomerases and proteases, which could otherwise cause additional DNA damage or alterations in chromatin structure. Inhibition of poly(ADP-ribose) polymerase by 3-amino-benzamide (3AB) in cells exposed to DNA-damaging agents would, according to this proposal, eliminate the regulatory role of ADP-ribosylation. When Chinese hamster ovary cells are cultured with methyl methanesulfonate (MMS) and 3AB, a synergistic increase in sister chromatid exchange frequency is observed. We investigated the regulatory role of poly(ADP-ribose) polymerase to see if topoisomerases or proteases are involved in this synergistic increase. Cells were exposed to MMS or the intercalating agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), 3AB, and either the topoisomerase inhibitor novobiocin or the protease inhibitor antipain. Neither novobiocin nor antipain affected the synergistic response of MMS and 3AB or the additive response of m-AMSA and 3AB. These results suggest that topoisomerases or proteases do not account for the effect of 3AB on sister chromatid exchange frequency after DNA damage.
mesh_terms: D000609:Aminoacridines / Q000633:toxicity; D000677:Amsacrine; D000818:Animals; D000976:Antipain / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004264:DNA Topoisomerases, Type I / Q000502:physiology*; D005260:Female; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009268:Nalidixic Acid / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D000609:Aminoacridines; D001549:Benzamides; D000677:Amsacrine; D009675:Novobiocin; D000976:Antipain; D009268:Nalidixic Acid; C025160:3-aminobenzamide; D008741:Methyl Methanesulfonate; D011065:Poly(ADP-ribose) Polymerases; D010447:Peptide Hydrolases; D004264:DNA Topoisomerases, Type I