Cell‐Cycle‐Dependent Active Thermal Bystander Effect (ATBE)

OBJECTIVE: To determine whether the active thermal bystander effect (ATBE) is cell-cycle dependent. MATERIALS AND METHODS: Dividing cells were directly heated for 10 minutes and co-cultured for 24 hours with different bystander cells. We compared the ATBE for dividing and non-dividing human fibroblasts, as well as for dividing human white preadipocytes (HWP) and non-dividing, mature differentiated human white adipocytes. ATBE was assessed as loss of cell viability of the bystander cells by using the MTT assay. Cell-cycle analysis was performed by using flow cytometry. RESULTS: Dividing fibroblasts and preadipocytes showed a significant ATBE (P < 0.008 and P < 0.05) with loss of cell viability of about 10% in the temperature range of 40-48°C. There was no significant difference between the extent of the bystander effect for these two cell populations (P = 0.30). In contrast, non-dividing fibroblasts and mature adipocytes did not generate any ATBE within this temperature range. There was a statistically significant difference in ATBE between dividing and non-dividing cell subpopulations for both fibroblasts (P = 0.003) and preadipocytes (P < 0.001) compared to their non-dividing counterparts. CONCLUSION: These results suggest that the ATBE is a cell-cycle-dependent process which requires actively dividing cells as receiving bystander cells. The cell-cycle dependency of the ATBE could have useful clinical applications in selectively targeting fast growing cells such as tumor cells. Whether the yield of the ATBE can be amplified by synchronizing the exposure to the ATBE with specific phases of the cell cycle remains subject to further investigation.