High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

Abstract

It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome – the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

Donor-Specific Cell-Based Assays in Studying Sensitivity to Low-Dose Radiation: A Population-Based Perspective

“…Collectively, the “omics” studies suggest that relatively long-lived (>24 h) changes in intracellular signaling should be evaluated in LDIR-related cellular responses. Studies focused on the analysis of certain signaling pathways confirmed that LDIR exposure indeed results in long-lived changes in intracellular signaling ( 60 – 63 ). However, a measurable effect that can serve as a biomarker of individual differences in response to low-dose radiation remains to be identified.…”

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation

“…Ionizing radiation is a classical mutagen and is capable of inducing various kinds of stable and unstable chromosomal aberrations (Vellingiri et al, 2014). Lowand high-dose exposures to ionizing radiation result in different signaling events at the molecular level, and may involve different response mechanisms (Zhang et al, 2014;von Neubeck et al, 2015). However, different LDIR-induced responses may also share the same signal transduction pathways (Tang and Loke, 2015).…”

Proteomic overview and perspectives of the radiation-induced bystander effects

“…The factors secreted by a human skin model were analysed following irradiation using a multidimensional LC-MS strategy [58]. A set of 135 proteins were identified as specifically modulated and potentially involved in a BR.…”