Tenofovir tra in folate-deient cells treated with alkylating

Jemmerson, X. Wang, Induction of apoptotic program in cell-free extracts: require- ment for dATP and cytochrome c , Cell 86 (1996)47?57. [29] S. Kamada, U. Kikkawa, Y. Tsujimoto, T. Hunter, Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein(s), J. Biol. Chem. 280 (2005)  Tenofovir 857?60. [30] A.S. Moreau, X. Jia, H.T. Ngo, X. Leleu, G. Oullivan, Y. Alsayed, A. Leontovich, K. Podar, J. Kutok, J. Daley, S. Lazo-Kallanian, E. Hatjiharissi, M.S. Raab, L. Xu, S.P. Treon, T. Hideshima, K.C. Anderson, I.M. Ghobrial

Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobuline- mia, Blood09 (2007) 4964?972. [31] K. Podar, M.S. Raab, J. Zhang, D. McMillin, I. Breitkreutz, Y.T. Tai, B.K. Lin, N. Munshi, T. Hideshima, D. Chauhan, K.C. Anderson, Targeting PKC in multiple myeloma: in vitro and in vivo eects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl), Blood09 (2007)669?677. [32] C. Querfeld, M.A. Rizvi, T.M. Kuzel, J. Guitart, A. Rademaker, S.S. Sabharwal, N.L. Krett, S.T. Rosen, The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway, J. Invest. Dermatol.26 (2006)641?1647. [33] G. Tabatabai, B. Frank, A. Wick, D. Lemke, G. von Kurthy, U. Obermuller, S. Heckl, G. Christ, M. Weller, W. Wick, Synergistic antiglioma activity of radiotherapy and enzastaurin, Ann. Neurol. 61  Tenofovir 147127-20-6 (2007)53?61. [34] A. Hurbin, J.L. Coll, L. Dubrez-Daloz, B. Mari, P. Auberger, C. Brambilla, M.C. Favrot, Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-depen- dent pathway in non-small cell lung cancer cells, J. Biol. Chem. 280 (2005)9757?9767. [35] M.A. McJilton, C. Van Sikes, G.G. Wescott, D. Wu, T.L. Foreman, C.W. Gregory, D.A.

Weidner, O. Harris Ford, A. Morgan Lasater, J.L. Mohler, D.M. Terrian, Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells, Oncogene 22 (2003) 7958?968. [36] H. Okhrimenko, W. Lu, C. Xiang, N. Hamburger, G. Kazimirsky, C. Brodie, Protein kinase C-epsilon regulates the apoptosis and survival of  buy Tenofovir glioma cells, Cancer Res. 65 (2005) 7301?309. 9 R.F. Branda et al. / Mutation Research 615 (2007)2?7 3 and schedules. We postulated that folic acid is a dietary colon [15] , and that methotrexate inhibits DNA excision constituent that may serve as a model for studies of the repair after exposure to EMS or ultraviolet irradiation interactions of diet and cancer chemotherapy. The possi- [14] . A possible mechanism for impaired DNA exci- ble relevance of this vitamin to chemotherapy outcome sion repair in folate-deient cells is mispairing and derives from the facts that folate nutritional status varies overloading of the repair system by excessive incorpo- widely in cancer patients [1,2] and that folate compounds ration of uracil into DNA. Folate deiency limits the have multiple effects on cellular metabolism. Folate methylation of dUMP to dTMP, resulting in extensive compounds play a central role in one-carbon transfers. incorporation of uracil into DNA by DNA polymerase Therefore they are essential co-factors for the synthesis [11?3] .

Repair of uracil residues utilizes excision repair of pyrimidine and purine nucleotides, for DNA methyla- [23,24] . Our studies characterizing the mutational spec- tion reactions, and for amino acid metabolism [3] . Folic tra in folate-deient cells treated with alkylating agents, acid deiency is associated with DNA strand breaks taken together with the work of others, support the fol- [4?] , chromosomal abnormalities [8?0] , increased lowing  disciplined study  mechanism to explain the synergy between folic uracil incorporation into DNA [5,7,11?3] , defective acid deiency and alkylating agents: (i) folate de? DNA repair [4,7,14,15] , increased somatic mutation ciency causes extensive uracil

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