P53 status influences regulation of HSPs and ribosomal proteins by PDTC and radiation.
Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that can act under varying conditions as an anti-oxidant or pro-oxidant. Utilizing microarrays, we determined the effect of PDTC +/- ionizing radiation (IR) on the expression of heat shock protein (HSP) genes in isolated B6/129 wild-type (WT) and p53-/- spleen cells. Extremely significant microarrays demonstrated that PDTC, but not IR, markedly up-regulated the expression of the majority of detectable HSP genes in WT and many to a significantly greater degree in p53-/- deficient cells. Determination of the glutathione/glutathione disulfide ratio indicated that PDTC was acting as a pro-oxidant under these conditions. From these data we conclude that the clinical use of "antioxidants" with radiotherapy or chemotherapy must be very carefully based on knowledge of the p53 status of their intended normal and tumor target cells.
Thompson
John S
JS
Veterans Affairs Medical Center, Lexington Kentucky, 40502, USA. jsthom1@uky.edu
Asmis
Reto
R
Glass
Judith
J
Liu
Hua
H
Wilson
Colin
C
Nelson
Brandy
B
Brown
Stephen A
SA
Stromberg
Arnold J
AJ
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012269:Ribosomal Proteins / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013859:Thiocarbamates / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D006360:Heat-Shock Proteins; D012269:Ribosomal Proteins; D013859:Thiocarbamates; D016159:Tumor Suppressor Protein p53; C066229:prolinedithiocarbamate; D011392:Proline