Selective protection of zidovudine-induced DNA-damage by the antioxidants WR-1065 and tempol

The cytokinesis‐block micronucleus cytome (CBMN) assay, introduced by Fenech, was used to demonstrate different types of DNA damage in MOLT‐3 human lymphoblastoid cells exposed to 10 μM zidovudine (AZT). In addition, we explored the cytoprotective potential of two antioxidants, WR‐1065 and Tempol, t...

Full description

Saved in:
Bibliographic Details
Published in:Environmental and molecular mutagenesis 2014-08, Vol.55 (7), p.566-572
Main Authors: Olivero, Ofelia A., Ongele, Michael O., Braun, Hannan M., Marrogi, Ariadna, Divi, Kathyiani, Mitchell, James B., Poirier, Miriam C.
Format: Article
Language:English
Subjects:
Antioxidants - chemistry
Apoptosis
CBMN assay
Cell Line, Tumor
Cell Nucleus - metabolism
Cell Proliferation
Cell Survival
Chromatin - chemistry
chromatin neoplasmic bridges
Chromosomes - ultrastructure
Cyclic N-Oxides - chemistry
Cytochalasin B - chemistry
cytome assay
DNA Damage
Humans
Mercaptoethylamines - chemistry
micronuclei
Micronucleus Tests
MOLT-3 cells
Mutagens - chemistry
Necrosis
nuclear buds
Radiation-Protective Agents - chemistry
Spin Labels
Zidovudine - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The cytokinesis‐block micronucleus cytome (CBMN) assay, introduced by Fenech, was used to demonstrate different types of DNA damage in MOLT‐3 human lymphoblastoid cells exposed to 10 μM zidovudine (AZT). In addition, we explored the cytoprotective potential of two antioxidants, WR‐1065 and Tempol, to decrease AZT‐induced genotoxicity. Binucleated cells, arrested by Cytochalasin B (Cyt B), were evaluated for micronuclei (MN), caused by DNA damage or chromosomal loss, and chromatin nucleoplasmic bridges (NPBs), caused by telomere attrition. Additionally, nuclear buds (NBUDs), caused by amplified DNA, and apoptotic and necrotic (A/N) cells were scored. We hypothesized that AZT exposure would increase the frequency of genotoxic end points, and that the antioxidants Tempol and WR‐1065 would protect against AZT‐induced genotoxicity. MOLT‐3 cells were exposed to 0 or 10 µM AZT for a total of 76 hr. After the first 24 hr, 0 or 5 µM WR‐1065 and/or 0 or 200 µM Tempol were added for the remainder of the experiment. For the last 28 hr (of 76 hr), Cyt B was added to arrest replication after one cell division, leaving a predominance of binucleated cells. The nuclear division index (NDI) was similar for all treatment groups, indicating that the exposures did not alter cell viability. MOLT‐3 cells exposed to AZT alone had significant (P 
ISSN:0893-6692
1098-2280
DOI:10.1002/em.21872