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Production of protein-associated DNA breaks by 8-methoxycaffeine, caffeine and 8-chlorocaffeine in isolated nuclei from L1210 cells: comparison with those produced by topoisomerase II inhibitors
- Source :
- Carcinogenesis. 12(10)
- Publication Year :
- 1991
-
Abstract
- 8-Methoxycaffeine (8-MOC) is a caffeine derivative, more potent than the parent compound, but very similar to caffeine in terms of induction of DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs) and DNA-protein crosslinks (DPCs). We have studied the capability of 8-MOC, caffeine and 8-chlorocaffeine (8-CC) of inducing SSBs, DSBs and DPCs, and we have compared 8-MOC with ellipticine, a typical inhibitor of DNA topoisomerase II. The DNA effects of 8-MOC appeared similar to those of ellipticine. In both cases SSBs, DSBs and DPCs were present in a similar ratio, and they were rapidly reversible after removal of the drug. The dose-response curve was bell-shaped for both compounds. In addition, 8-MOC, caffeine and 8-CC were capable of inhibiting DSBs induced by ellipticine. These results were obtained at the level of L1210 cell nuclei. In spite of these functional similarities, 8-MOC, caffeine and 8-CC were unable to stimulate the formation of a cleavable complex by purified L1210 topoisomerase II (p170 form) when SV40 DNA and human c-myc DNA were used as substrate. These methylated oxypurines could be active on a different form of topoisomerase II, or, alternatively, they could be active only in the natural chromatin 'milieu' within the nucleus.
- Subjects :
- Cancer Research
DNA damage
Genes, myc
Simian virus 40
Biology
DNA-binding protein
Proto-Oncogene Proteins c-myc
chemistry.chemical_compound
Mice
Caffeine
Tumor Cells, Cultured
Animals
Humans
Topoisomerase II Inhibitors
Drug Interactions
Ellipticines
Leukemia L1210
chemistry.chemical_classification
Cell Nucleus
Topoisomerase
General Medicine
DNA, Neoplasm
Molecular biology
Chromatin
DNA-Binding Proteins
Enzyme
DNA Topoisomerases, Type II
chemistry
Biochemistry
DNA, Viral
biology.protein
Autoradiography
Topoisomerase-II Inhibitor
DNA
DNA Damage
Subjects
Details
- ISSN :
- 01433334
- Volume :
- 12
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....42a27b44d2e72fe75eadac5f4f133006