Bystander effect produced by radiolabeled tumor cells in vivo

Abstract

The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in an animal, the ability of 5-[¹²⁵I]iodo-2′-deoxyuridine (¹²⁵IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing s.c. in nude mice has been investigated. When mice are injected with a mixture of human colon LS174T adenocarcinoma cells and LS174T cells prelabeled with lethal doses of DNA-incorporated ¹²⁵I, a distinct inhibitory effect on the growth of s.c. tumor (derived from unlabeled cells) is observed. Because (i) the ¹²⁵I present within the cells is DNA-bound, (ii) ≈99% of the electrons emitted by the decaying ¹²⁵I atoms have a subcellular range (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is in vivo by factor(s) present within and/or released from the ¹²⁵IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures.