Effect of 5-hydroxytryptamine (serotonin) receptor inhibitors on the radiation-induced bystander effect

Purpose: To test the importance of serotonin as a signaling molecule involved in the production and response of radiation-induced bystander effects. Materials and methods: HPV-G human keratinocyte cultures were spiked with various concentrations of Granisetron or Ketanserin and subject to either 0 Gy or 0.5 Gy X-irradiation to observe the inhibitor's effects on bystander signal production. Medium from these cultures was harvested and introduced to non-irradiated cultures of the same cell line to determine the clonogenic bystander response. Separate HPV-G cultures were set up for subsequent calcium measurements in response to irradiated cell conditioned medium (ICCM) in the presence or absence of Granisetron in an attempt to block bystander signal response. Results: Granisetron and Ketanserin produced a dose-dependent propagation of the bystander effect in recipient cultures. Granisetron completely abolished the characteristic calcium pulse observed when non-irradiated cultures are exposed to irradiated cell medium in the presence of this drug. Conclusions: Serotonin-dependent mechanisms appear to be involved in bystander signal production and response to radiation in this system.