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The Lipophilicity of Phorbol Esters as a Critical Factor in Determining the Pattern of Translocation of Protein Kinase C δ Fused to Green Fluorescent Protein*
The results indicate that lipophilicity of phorbol esters is a critical factor contributing to differential PKC δ localization and thereby potentially to their different biological activities.
Epidoxoform: a hydrolytically more stable anthracycline-formaldehyde conjugate toxic to resistant tumor cells.
Epidoxoform in equilibrium with its hydrolysis products is greater than 25-fold more toxic to resistant cells with respect to epidoxorubicin, and greater than 120-foldMore toxic to MCF-7/ADR resistant cells than epidoxoforms in equilibrium.
Doxoform and Daunoform: anthracycline-formaldehyde conjugates toxic to resistant tumor cells.
Daunoform reacts with the self-complementary deoxyoligonucleotide (GC)4 faster than the combination of daunorubicin and formaldehyde at an equivalent concentration to given drug-DNA adducts, and in spite of hydrolytic instability, Doxoform is 150-fold more toxic to MCF-7 human breast cancer cells and 10000-foldMore toxic toMCF- 7/ADR resistant cells.
Nuclear targeting and nuclear retention of anthracycline-formaldehyde conjugates implicates DNA covalent bonding in the cytotoxic mechanism of anthracyclines.
The results implicate drug-DNA covalent bonding in the tumor cell toxicity mechanism of these anthracyclines.
Mass spectrometric measurement of formaldehyde generated in breast cancer cells upon treatment with anthracycline antitumor drugs.
- S. Kato, P. Burke, D. Fenick, D. Taatjes, V. Bierbaum, T. Koch
- Chemistry, BiologyChemical research in toxicology
- 5 May 2000
The results support a mechanism for drug cytotoxicity which involves drug induction of metabolic processes leading to formaldehyde production followed by drug utilization of formaldehyde to virtually cross-link DNA.
A redox pathway leading to the alkylation of nucleic acids by doxorubicin and related anthracyclines: application to the design of antitumor drugs for resistant cancer.
- D. Taatjes, D. Fenick, G. Gaudiano, T. Koch
- Biology, ChemistryCurrent pharmaceutical design
- 1 June 1998
Doxorubicin has been a constituent of antitumor drug protocols for a broad spectrum of cancers for more than two decades and has potential for the treatment of resistant cancer.
MODEL STUDIES OF DNA PHOTOREPAIR: REDUCTION POTENTIALS OF THYMINE AND CYTOSINE CYCLOBUTANE DIMERS MEASURED BY FLUORESCENCE QUENCHING
The interactions of various pyrimidines (1,3-dimethylthymine, DMT, 1,3-bis(N4,N4-dimethylcytosin-1-yl)propane, DMC) and their corresponding cis-syn cyclobutane dimers (DMTD and DMCD) with a series of…
Synthesis and Photochemical Cleavage of Cis-Syn Pyrimidine Cyclobutane Dimer Analogs
Free Radical Rearrangements in Uracil Derivatives
As part of an effort to develop general probes for radical reactions involving DNA bases, several uracil derivatives were synthesized. The rates of the cyclopropyl carbinyl rearrangement in these…