Induction of DNA strand breaks by H/sub 2/O/sub 2/ and PMA

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5317438

Schraufstaetter, I U; Hyslop, P A; Jackson, J; Cochrane, C G

The authors have previously reported that oxidants induce cell lysis in P388Dl cells and lymphocytes which is caused by activation of poly-ADP-ribose polymerase leading to NAD and ATP depletion. Generally, poly-ADP-ribose polymerase is activated in the presence of single stranded DNA. Here they report that small concentrations of H/sub 2/O/sub 2/ (1-2 nmoles/min/ 2 x 10/sup 6/ cells produced by glucose oxidase-glucose) caused DNA strand breaks in human peripheral lymphocytes, P388Dl cells and freshly isolated rabbit pulmonary endothelial cells. DNA strand breaks were determined by an alkaline unwinding technique. To induce DNA strand breaks in rabbit alveolar macrophages or human monocytes higher concentrations of H/sub 2/O/sub 2/ (about 100 nmoles/ml) were necessary, presumably due to high activity of H/sub 2/O/sub 2/ catabolizing enzymes. Peripheral lymphocytes, which do not produce H/sub 2/O/sub 2/, did not form DNA strand breaks in the presence of 100 ng/ml phorbol myristate acetate (PMA). Few strand breaks were observed in monocytes (1.25 x 10/sup 6/ cells/ml) stimulated with PMA, since the concentration of H/sub 2/O/sub 2/ present under these conditions (20-30 nmoles) was insufficient to induce strand breaks in the cells. However, when lymphocytes and monocytes were mixed together in a ratio of 3:1, and exposed to PMA, DNA strand breaks occurred equivalent to those seen with 40 nmoles H/sub 2/O/sub 2/. Their results indicate that oxidants produced by stimulated leukocytes can induce DNA damage in neighboring cells.

• Research Organization: Scripps Clinic and Research Foundation, La Jolla, CA
• OSTI ID: 5317438
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARCINOGENS
CONNECTIVE TISSUE CELLS
DNA
ENDOTHELIUM
ESTERS
GENETIC EFFECTS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
LEUKOCYTES
LUNGS
LYMPHOCYTES
LYSIS
MACROPHAGES
MAMMALS
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEROXIDES
PHAGOCYTES
PHORBOL ESTERS
RABBITS
RESPIRATORY SYSTEM
SOMATIC CELLS
STRAND BREAKS
TISSUES
VERTEBRATES