Faculty Collaboration Database

Activated murine neutrophils induce unscheduled DNA synthesis in B lymphocytes. Mutat Res 1993 Jan;293(2):173-86

Date

01/01/1993

Pubmed ID

7678145

DOI

10.1016/0921-8777(93)90068-r

Abstract

Activated neutrophils induce DNA damage in neighboring cells by secreting reactive oxygen compounds into the extracellular milieu. Repair of this damage is required to prevent mutagenesis and neoplastic transformation. Conditions were established to detect the activation of excision-repair pathways (unscheduled DNA synthesis) by measuring stimulated thymidine uptake in target B lymphocytes exposed to activated neutrophils. Murine neutrophils were cocultured in serum-free medium with splenic B cells or with murine plasmacytoma cells for 2 h. Unscheduled DNA synthesis in the B cells was detected at neutrophil:target cell ratios of 1:1 to 4:1 when the neutrophils were activated with phorbol myristate acetate. Reagent H2O2 alone (> or = 6 microM) also induced UDS whereas HOCl (up to 4 mM) did not. No repair synthesis was observed within the neutrophils themselves. Control experiments indicated that the induction of UDS by neutrophils and H2O2 was not due to formation of a stable genotoxic compound from HU. On the contrary, scavenging of free H2O2 by HU probably lowered the levels of UDS that could be detected by these agents. Induction of unscheduled DNA synthesis by neutrophils and H2O2 occurred under conditions of less cytostasis than was found with other DNA-damaging agents such as 4-nitroquinoline 1-oxide or gamma-irradiation. This may reflect a heightened responsiveness of the cells to repair of damage from physiological oxidants. The results demonstrate that DNA damage induced by reactive oxygen intermediates can be repaired by nucleotide excision-repair pathways.

Author List

Janz S, Shacter E

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
B-Lymphocytes
Cell Separation
Cells, Cultured
DNA Repair
Hydrogen Peroxide
In Vitro Techniques
Mice
Mice, Inbred Strains
Neutrophils
Oxidants
Reactive Oxygen Species
Terpenes