Inhibition of topoisomerase II activity in repair-proficient CHO K1 cells by 2-[(aminopropyl)amino]ethanethiol (WR-1065)
The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation protector under in vitro conditions when it is administered 30 min prior to radiation exposure at a concentration of 4 mM to repair-proficient Chinese hamster ovary Kl cells (i.e., a dose modification factor of 1.4). In contrast, the DNA double-strand break, repair-deficient Chinese hamster ovary xrs-5 cell line is not protected under these conditions (i.e., a dose modification factor of 1.0). Topoisomerase (topo) I and II activities and protein contents were measured in both Kl and xrs-5 cell lines and were found to be similar in magnitude. Neither exposure to radiation, to WR-1065, or to both affected these variables in xrs-5 cells. WR 1065 was effective, however, in reducing topo 11 activity by a factor of 2 in the repair-proficient Kl cell line. Topo II protein content, however, was not affected by these exposure conditions. One of several mechanisms of radiation protection attributed to aminothiol compounds has been their ability to affect enzymatic reactions involved in DNA synthesis, repair, and cell cycle progression. These results demonstrate a modifying effect by 2-[(aminopropyl)amino]ethanethiol on a specific nuclear enzyme (i.e., type H topoisomerase), which is involved in DNA synthesis. These results also suggest that differences do exist between the topo 11 enzymes isolated from the parent repair-proficient Kl and the DNA double-strand break, repair-deficient xrs-5 mutant cell lines.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States); National Cancer Inst., Bethesda, MD (United States)
- DOE Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 10184593
- Report Number(s):
- ANL/BIM/PP-77686; ON: DE93040891; CNN: Grant CA 37435; TRN: 93:021803
- Resource Relation:
- Other Information: PBD: Sep 1992
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
DNA HELICASES
BIOCHEMICAL REACTION KINETICS
GENE MUTATIONS
DNA REPAIR
MOLECULAR BIOLOGY
RADIOPROTECTIVE SUBSTANCES
ENZYME INHIBITORS
CHO CELLS
STRAND BREAKS
X RADIATION
BIOLOGICAL RADIATION EFFECTS
560120
550200
RADIATION EFFECTS ON BIOCHEMICALS, CELLS, AND TISSUE CULTURE
BIOCHEMISTRY