Potentiation of sister chromatid exchange by 3-aminobenzamide is not modulated by topoisomerases or proteases
Poly(ADP-ribose) is synthesized in response to DNA strand breaks and covalently modifies numerous intracellular proteins. The authors 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. The authors 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.
- Research Organization:
- Univ. of California, San Francisco
- DOE Contract Number:
- AC03-76SF01012
- OSTI ID:
- 5148616
- Journal Information:
- Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 8:4; ISSN ENMUD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMAL CELLS
BIOLOGICAL EFFECTS
CHO CELLS
CHROMOSOMAL ABERRATIONS
DNA
ENZYME ACTIVITY
ENZYMES
ESTERS
HYDROLASES
ISOMERASES
METHYL METHANESULFONATE
MUTAGENS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HYDROLASES
SISTER CHROMATID EXCHANGES
STRAND BREAKS
SULFONIC ACID ESTERS