Bystander effect in tumor cells produced by Iodine-125 labeled human lymphocytes

Int J Radiat Biol. 2012 Dec;88(12):1019-27. doi: 10.3109/09553002.2012.702297. Epub 2012 Jul 9.

Abstract

Purpose: To investigate the ability of human lymphocytes labeled with DNA-incorporated (125)I to exert an inhibitory (antiproliferative) bystander effect on co-cultured human colon adenocarcinoma LS174T cells in vitro.

Materials and methods: Human peripheral blood lymphocytes were stimulated to synthesize DNA in the presence of phytohemagglutinin (PHA) and labeled with 5-[(125)I]iodo-2'-deoxyuridine. Human colon adenocarcinoma LS174T cells were co-cultured with the (125)I-labeled lymphocytes in various ratios for 5 days and the proliferation of the LS174T cells was assessed. Further, the supernatant media from these co-cultures were: (i) Transferred to LS174T cells and their proliferation measured after 5 days, (ii) used to assess the clonogenic survival of LS174T cells, and (iii) screened for factors that suppress growth.

Results: A significant reduction in the proliferation of LS174T cells was observed when co-cultured either with (125)I-labeled lymphocytes (56 ± 3.5%) or the supernatant media (52.5 ± 1.3%) obtained from these co-cultures. Clonogenic survival of LS174T cells grown in the supernatant media corroborated the decrease in tumor cell growth.

Conclusion: The observed reduction in the proliferation of LS174T cells in presence of (125)I-labeled lymphocytes or media obtained from such co-cultures can be attributed to an inhibitory (antiproliferative) bystander effect, probably mediated by factor(s) released from the dying (125)I-labeled lymphocytes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bystander Effect / radiation effects*
  • Cell Line, Tumor
  • Cell Proliferation / radiation effects
  • Coculture Techniques
  • Humans
  • Idoxuridine / metabolism
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / metabolism
  • Iodine Radioisotopes / metabolism
  • Isotope Labeling
  • Lymphocytes / cytology*
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • Interleukin-1alpha
  • Interleukin-1beta
  • Iodine Radioisotopes
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Idoxuridine