Transient genome-wide transcriptional response to low-dose ionizing radiation in vivo in humans

Abstract

Purpose: The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy.

Methods and materials: RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.0 array. Data analysis was performed on selected gene groups and pathways.

Results: Nineteen gene groups and seven gene pathways that had been shown to be radiation responsive were analyzed. Of these, nine gene groups showed significant transient transcriptional changes in the human tissue samples, which returned to baseline by 24 hours postexposure.

Conclusions: Low doses of ionizing radiation on full-thickness human skin produce a definable temporal response out to 24 hours postexposure. Genes involved in DNA and tissue remodeling, cell cycle transition, and inflammation show statistically significant changes in expression, despite variability between patients. These data serve as a reference for the temporal dynamics of ionizing radiation response following low-dose exposure in healthy full-thickness human skin.

Fig. 1

Time course of median transcriptional responses for the zinc finger protein gene group. Each line shows the change in expression from the initial time point, which is set to zero. The other time point values are differences in median expression between that time point and time 0. It can be seen that all patients exhibited a similar pattern of up-regulation followed by a falling off toward the original expression level. For this gene group, all five patients (P1–P5) showed transient up-regulation by our test, as did the cohort as a whole.