Kinetics of cell-free DNA in response to exogenous and exertional heating in healthy young men.

Purpose: Circulating cell-free DNA (cfDNA) is recognized as a relevant biomarker for monitoring the effects of various physiological and pathophysiological factors. To identify the effect of body temperature, we investigated the kinetics of cfDNA in response to two forms of heating.

Methods: In a randomized crossover design, twelve healthy young males cycled at 60% of their maximum oxygen uptake (VO_2max) (exertional heating) and conducted lower-body immersion in hot water (43-44°C) (exogenous heating) until their rectal temperature (T_re) reached 39°C. EDTA blood samples were collected at each time point T_re increased and decreased by 0.5°C, to determine the concentrations of cfDNA, epinephrine (Epi), norepinephrine (NE), prolactin (PRL), as well as subjective sensation, and heart rate.

Results: Linear mixed model analyses revealed a strong significant interaction effect for cfDNA (T_re × heating modality, F (6, 135.95) = 7.51, P < 0.001), with a significant 1.76-fold increase of cfDNA in response to exogenous heating and a 5.72-fold increase in response to exertional heating (P < 0.05). Significant interaction effects were detected for NE (F (6, 109.80) = 8.0683, P < 0.001), and PRL (F (6, 120.92) = 2.2746, P = 0.041), but not Epi. Repeated measures correlation (r_rm) showed strong correlations between cfDNA and core temperature in exertional heating (r_rm = 0.89), as well as exogenous heating (r_rm = 0.75).

Conclusion: Our findings demonstrate that an increase in rectal temperature induces physiological stress, which triggers the release of cfDNA, however, at a significantly lower level than exertional heating, suggesting that mechanical stress has a greater influence on the release.