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


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.


CONCLUSIONS
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.
Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Omar
O
Mamlouk
Pichumani
P
Balagurumoorthy
Ketai
K
Wang
S James
SJ
Adelstein
Amin I
AI
Kassis
D024201:Bystander Effect / Q000528:radiation effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D018920:Coculture Techniques; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D007553:Isotope Labeling; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D007457:Iodine Radioisotopes; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D007065:Idoxuridine