{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:45:59Z","timestamp":1760852759866},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,3,18]],"date-time":"2002-03-18T00:00:00Z","timestamp":1016409600000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Exp Therapeutics"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>A variety of anticalmodulin drugs can increase the cytotoxicity of bleomycin, a DNA damaging cancer chemotherapeutic. The combination has been shown to produce greater than expected DNA damage compared wot what was observed with either drug alone. Promising preclinical results led to Phase I and Phase II trials of trifluoperazine and bleomycin, which revealed activity in non\u2010Hodgkin's lymphoma. Despite the unique activity of the combination, the mechanism underlying the DNA damaging effect remained poorly understood. In several systems, DNA damage leads to the induction of programmed cell death or apoptosis, which is characterized by interoligonucleosomal cleavage of DNA. To determine whether the activity of the combination of bleomycin with trifluoperazine was due to induction of apoptosis, we exposed L1210 leukemic lymphocytes to bleomycin in the presence or absence of trifluoperazine. The combination produced DNA laddering, cellular shrinkage, and chromatin condensation typical of programmed cell death. Cell cycle analyses revealed a blockade of cells in G2\/M, suggesting the presence of mutant p53, which was confirmed by immunoanalysis. In addition, L1210 cells were found not to overexpress Bcl\u20102 in the presence or absence of drugs. These results indicate that the enhancement of bleomycin induced DNA damage by trifluoperazine is mediated, at least in part, through the induction of apoptosis.<\/jats:p>","DOI":"10.1046\/j.1359-4117.2002.01002.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T05:04:35Z","timestamp":1047445475000},"page":"19-26","source":"Crossref","is-referenced-by-count":13,"title":["Augmentation of apoptosis by the combination of bleomycin with trifluoperazine in the presence of mutant p53"],"prefix":"10.1111","volume":"2","author":[{"given":"Gregory F.","family":"Sullivan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne","family":"Garcia\u2010Welch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Lutzker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William N.","family":"Hait","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,3,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1986.4.6.994"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(85)90120-1"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00258116"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(85)90374-0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6203171"},{"key":"e_1_2_6_7_2","first-page":"387","article-title":"Enhanced bleomycin\u2010induced DNA damage and cytotoxicity with calmodulin antagonists.","volume":"27","author":"Lazo JS","year":"1985","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_8_2","first-page":"2236","article-title":"Increased lethality of calmodulin antagonists and bleomycin to human bone marrow and bleomycin\u2010resistant malignant cells.","volume":"46","author":"Lazo JS","year":"1986","journal-title":"Cancer Res"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(86)90173-2"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.4.246"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00435836"},{"key":"e_1_2_6_12_2","first-page":"6636","article-title":"The effect of calmodulin inhibitors with bleomycin on the treatment of patients with high grade gliomas.","volume":"50","author":"Hait WN","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.12a.2277"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00048059"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)62312-8"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.3.1415"},{"key":"e_1_2_6_17_2","first-page":"2928","article-title":"Transfection with a Bcl\u20102 expression vector protects transplanted bone marrow from chemotherapy\u2010induced myelosuppression.","volume":"54","author":"Kondo S","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.5.2697"},{"key":"e_1_2_6_19_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1128\/jvi.59.2.444-452.1986","article-title":"Monoclonal antibody analysis of p53 expression in normal and transformed cells.","volume":"59","author":"Yewdell JW","year":"1986","journal-title":"J Virol"},{"key":"e_1_2_6_20_2","first-page":"6304","article-title":"Participation of p53 protein in the cellular response to DNA damage.","volume":"51","author":"Kastan MB","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0020-711X(87)90311-9"},{"key":"e_1_2_6_22_2","first-page":"581","article-title":"Mechanism by which psychotropic drugs inhibit adenosine cyclic 3,5\u2010monophosphate phosphodiesterase of brain.","volume":"12","author":"Levin RM","year":"1976","journal-title":"Mol Parmacol"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"18580","DOI":"10.1016\/S0021-9258(18)55102-4","article-title":"Identification, purification, and characterization of a calcium\u2010dependent endonuclease (NUC18) from apoptotic rat thymocytes. 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