Polymorphic radiation sensitivity of human natural killer activity: Possible role of DNA strand breakage

Bernice Schacter, Susan Hansal, Janet Arno, Mark J. LeVine

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Natural killer (NK) activity of human mononuclear cells is sensitive to inhibition by radiation, under the control of polymorphic X linked genes. In order to define the mechanism of this inhibition, we have evaluated the ability of treatments known to damage DNA to inhibit NK activity. The alkylating agents streptozotocin (SZ) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) were potent inhibitors of NK activity. Further, a specific competitive inhibitor of adenosine diphosphoribosyl polymerase (ADPRP), 3-aminobenzamide, was able to prevent inhibition by γ-radiation, UV radiation, and the two alkylating drugs, SZ and MNNG, suggesting the ADPRP, known to be activated by DNA strand breakage, mediates the inhibition by these treatments. NK activity of radioresistant subjects was somewhat more resistant to inhibition by SZ or UVR when compared to radiosensitive NK activity but neither of these treatments gave the clear phenotypic distinction of γ-radiation, suggesting that chemical strand breakage does not precisely model γ-radiation and also that the mechanism of UVR inhibition may differ from that of γ-radiation. These results indicate a role for activation of ADPRP in the inhibitory effect of UV and γ-radiation on human NK activity and suggest that the biochemical basis for polymorphism in the sensitivity of NK activity to γ-radiation will be found in the sensitivity to ADPRP activation or the level of activation of this enzyme, known to be the key to DNA repair.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalHuman Immunology
Volume14
Issue number1
DOIs
StatePublished - Sep 1985

Keywords

  • ADPRP adenosine diphosphoribosylpolymerase 3AB 3 aminobenzamide DMSO dimethylsulfoxide E/T effector/target Fcs fetal calf serum HRPMI hepes buffered RPMI1640 IFN interferon IL-2 interleukin-2 mJ/cm millijoules/square ce centimeter

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Polymorphic radiation sensitivity of human natural killer activity: Possible role of DNA strand breakage'. Together they form a unique fingerprint.

  • Cite this