title: The purinergic P2Y14 receptor axis is a molecular determinant for organism survival under in utero radiation toxicity.
abstract: In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Kook
authors.forename: J S
authors.initials: JS
authors.lastname: Cho
authors.forename: A
authors.initials: A
authors.lastname: Morrison
authors.forename: E
authors.initials: E
authors.lastname: Wiener
authors.forename: S B
authors.initials: SB
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Scadden
authors.forename: B-C
authors.initials: BC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001284:Atrophy / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D006849:Hydrocephalus / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000517:prevention & control*; D011836:Radiation Tolerance; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics*; D058470:Receptors, Purinergic P2Y; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology* / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: C509795:P2ry14 protein, mouse; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; D014532:Uridine Diphosphate Glucose