Palmitoyl ascorbic acid 2-glucoside has the potential to protect mammalian cells from high-LET carbon-ion radiation

Alexis H Haskins,Takamitsu A Kato,Dylan J Buglewicz,Hirokazu Hirakawa,Yasushi Aizawa,Akira Fujimori

doi:10.1038/s41598-018-31747-1

Abstract

DMSO, glycerol, and ascorbic acid (AA) are used in pharmaceuticals and known to display radioprotective effects. The present study investigates radioprotective properties of novel glyceryl glucoside, ascorbic acid 2-glucoside, glyceryl ascorbate, and palmitoyl ascorbic acid 2-glucoside (PA). Gamma-rays or high-LET carbon-ions were irradiated in the presence of tested chemicals. Lambda DNA damage, cell survival, and micronuclei formation of CHO cells were analyzed to evaluate radioprotective properties. Radiation-induced Lambda DNA damage was reduced with chemical pre-treatment in a concentration-dependent manner. This confirmed tested chemicals were radical scavengers. For gamma-irradiation, enhanced cell survival and reduction of micronuclei formation were observed for all chemicals. For carbon-ion irradiation, DMSO, glycerol, and PA displayed radioprotection for cell survival. Based on cell survival curves, protection levels by PA were confirmed and comparable between gamma-rays and high-LET carbon-ions. Micronuclei formation was only decreased with AA and a high concentration of glycerol treatment, and not decreased with PA treatment. This suggests that mechanisms of protection against high-LET carbon-ions by PA can differ from normal radical scavenging effects that protect DNA from damage.

Highlights

Ionizing radiation (IR) of living cells is a known cause of cancer, mutations, and aging[1,2,3,4]
The current study explored the radioprotective properties of DMSO, glycerol, Glyceryl glucoside (GG), ascorbic acid (AA), 2 G, glycerol ascorbic acid (GA), and palmitoyl ascorbic acid 2-glucoside (PA) (Fig. 1) by investigating Chinese hamster ovary (CHO) cells and Lambda DNA in terms of cell survival, micronuclei formation, and DNA damage after irradiation of gamma-rays and high-LET carbon-ions
Cells were pre-treated 0.5 hour prior to irradiation, which was sufficient for DMSO, glycerol, and AA to display radioprotective properties

Summary

Introduction

Ionizing radiation (IR) of living cells is a known cause of cancer, mutations, and aging[1,2,3,4]. Dimethyl sulfide (DMSO), glycerol, and ascorbic acid (AA) are well known radical scavengers[5,6,7,8,9,10]. They display cellular toxicity with continuous exposure[11,12,13]. Previous studies showed AA modified chemicals maintained their antioxidant properties and are expected to be potential practical radioprotectors[9,21,22]. We hypothesized that chemically modified classical radioprotectors are radical scavengers and have the potential to display radioprotective effects. The current study explored the radioprotective properties of DMSO, glycerol, GG, AA, 2 G, GA, and PA (Fig. 1) by investigating CHO cells and Lambda DNA in terms of cell survival, micronuclei formation, and DNA damage after irradiation of gamma-rays and high-LET carbon-ions

Methods

Results

Conclusion