RLIP76 is a major determinant of radiation sensitivity

Sanjay Awasthi, Sharad S. Singhal, Sushma Yadav, Jyotsana Singhal, Kenneth Drake, Aalok Nadkar, Ewa Zajac, Dilki Wickramarachchi, Nancy Rowe, Adly Yacoub, Paul Boor, Seema Dwivedi, Paul Dent, Wendy E. Jarman, Berchmans John, Yogesh C. Awasthi

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6022-6028
Number of pages7
JournalCancer Research
Volume65
Issue number14
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Awasthi, S., Singhal, S. S., Yadav, S., Singhal, J., Drake, K., Nadkar, A., Zajac, E., Wickramarachchi, D., Rowe, N., Yacoub, A., Boor, P., Dwivedi, S., Dent, P., Jarman, W. E., John, B., & Awasthi, Y. C. (2005). RLIP76 is a major determinant of radiation sensitivity. Cancer Research, 65(14), 6022-6028. https://doi.org/10.1158/0008-5472.CAN-05-0968