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Publication : RLIP76 is a major determinant of radiation sensitivity.

First Author  Awasthi S Year  2005
Journal  Cancer Res Volume  65
Issue  14 Pages  6022-8
PubMed ID  16024601 Mgi Jnum  J:100087
Mgi Id  MGI:3586931 Doi  10.1158/0008-5472.CAN-05-0968
Citation  Awasthi S, et al. (2005) RLIP76 is a major determinant of radiation sensitivity. Cancer Res 65(14):6022-8
abstractText  RLIP76 (RALBP1) is a glutathione-conjugate transporter that is a critical component of clathrin-coated pit-mediated endocytosis, as well as in stress responses. In cultured cells, it provides protection from stressors including heat, oxidant chemicals, chemotherapeutic agents, UV irradiation, and X-irradiation. Here, we show marked reduction in glutathione conjugate transport capacity and stepwise increase in radiation sensitivity associated with heterozygous or homozygous loss of the RLIP76 gene in mice. Survival after radiation in homozygous knockout animals was significantly shorter than either the heterozygous knockouts or the wild type. Delivery of recombinant RLIP76 to mice lacking RLIP76 via a liposomal delivery system rescued radiation sensitivity. Furthermore, treatment of wild-type mice with RLIP76-containing liposomes conferred resistance to radiation. These findings suggest that inhibiting RLIP76 could be used for sensitization to radiation during cancer therapy and that RLIP76 liposomes could be radioprotective agents useful for treatment of iatrogenic or catastrophic radiation poisoning.
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