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dc.contributor.authorNewton, K
dc.contributor.authorStrasser, A
dc.date.accessioned2020-12-21T01:05:04Z
dc.date.available2020-12-21T01:05:04Z
dc.date.issued2000-01-03
dc.identifier.citationNewton, K. & Strasser, A. (2000). Ionizing radiation and chemotherapeutic drugs induce apoptosis in lymphocytes in the absence of Fas or FADD/MORT1 signaling: Implications for cancer therapy. JOURNAL OF EXPERIMENTAL MEDICINE, 191 (1), pp.195-200. https://doi.org/10.1084/jem.191.1.195.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/256359
dc.description.abstractIonizing radiation and cytotoxic drugs used in the treatment of cancer induce apoptosis in many cell types, including tumor cells. It has been reported that tumor cells treated with anticancer drugs increase surface expression of Fas ligand (FasL) and are killed by autocrine or paracrine apoptosis signaling through Fas (Friesen, C., I. Herr, P.H. Krammer, and K.-M. Debatin. 1996. Nat. Med. 2:574-577). We show that lymphocytes that cannot be killed by FasL, such as those from Fas-deficient lpr mice or transgenic mice expressing a dominant negative mutant of Fas-associated death domain protein (FADD/MORT1), are as sensitive as normal lymphocytes to killing by gamma radiation or the cytotoxic drugs cis-platin, doxorubicin, and etoposide. In contrast, p53 deficiency or constitutive expression of Bcl-2 markedly increased the resistance of lymphocytes to gamma radiation or anticancer drugs but had no effect on killing by FasL. Consistent with these observations, lpr and wild-type T cells both had a reduced capacity for mitogen-induced proliferation after drug treatment, whereas bcl-2 transgenic or p53-deficient T cells retained significant clonogenic potential. These results demonstrate that apoptosis induced by ionizing radiation or anticancer drugs requires p53 and is regulated by the Bcl-2 protein family but does not require signals transduced by Fas and FADD/MORT1.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleIonizing radiation and chemotherapeutic drugs induce apoptosis in lymphocytes in the absence of Fas or FADD/MORT1 signaling: Implications for cancer therapy
dc.typeJournal Article
dc.identifier.doi10.1084/jem.191.1.195
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume191
melbourne.source.issue1
melbourne.source.pages195-200
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1218465
melbourne.contributor.authorStrasser, Andreas
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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