Interstrand cross-linking by Adriamycin in nuclear and mitochondrial DNA of MCF-7 cells Export

@article{citeulike:4882281, abstract = {Activation of Adriamycin by formaldehyde leads to the formation of drug-DNA adducts in vitro and these adducts stabilise the DNA to such a degree that they function as virtual interstrand cross-links. The formation of these virtual interstrand cross-links by Adriamycin was investigated in MCF-7 cells using a gene-specific interstrand cross-linking assay. Cross-linking was measured in both the nuclear-encoded DHFR gene and in mitochondrial DNA (mtDNA). Cross-link formation increased linearly with Adriamycin concentration following a 4 h exposure to the drug. The rate of formation of Adriamycin cross-links in each of the genomes was similar, reaching maximal levels of 0.55 and 0.4 cross-links/10 kb in the DHFR gene and mtDNA respectively, following exposure to 20 {micro}M Adriamycin for 8 h. The interstrand cross-link was short lived in both DNA compartments, with a half-life of 4.5 and 3.3 h in the DHFR gene and mtDNA respectively. The kinetics of total Adriamycin adduct formation, detected using [14C]Adriamycin, was similar to that of cross-link formation. Maximal adduct levels (30 lesions/10 kb) were observed following incubation at 20 {micro}M drug for 8 h. The formation of such high levels of adducts and cross-links could therefore be expected to contribute to the mechanism of action of Adriamycin. 10.1093/nar/28.4.1019}, author = {Cullinane, Carleen and Cutts, Suzanne M. and Panousis, Con and Phillips, Don R.}, citeulike-article-id = {4882281}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/28.4.1019}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/cgi/content/abstract/28/4/1019}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/10648796}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=10648796}, day = {15}, doi = {10.1093/nar/28.4.1019}, journal = {Nucl. Acids Res.}, keywords = {adriamycin, cross-link, damage, dna, doxorubicin, interstrand}, month = {February}, number = {4}, pages = {1019--1025}, posted-at = {2009-06-17 17:42:27}, priority = {2}, title = {Interstrand cross-linking by Adriamycin in nuclear and mitochondrial DNA of MCF-7 cells}, url = {http://dx.doi.org/10.1093/nar/28.4.1019}, volume = {28}, year = {2000} }

TY - JOUR ID - citeulike:4882281 L3 - citeulike-article-id:4882281 N2 - Activation of Adriamycin by formaldehyde leads to the formation of drug-DNA adducts in vitro and these adducts stabilise the DNA to such a degree that they function as virtual interstrand cross-links. The formation of these virtual interstrand cross-links by Adriamycin was investigated in MCF-7 cells using a gene-specific interstrand cross-linking assay. Cross-linking was measured in both the nuclear-encoded DHFR gene and in mitochondrial DNA (mtDNA). Cross-link formation increased linearly with Adriamycin concentration following a 4 h exposure to the drug. The rate of formation of Adriamycin cross-links in each of the genomes was similar, reaching maximal levels of 0.55 and 0.4 cross-links/10 kb in the DHFR gene and mtDNA respectively, following exposure to 20 {micro}M Adriamycin for 8 h. The interstrand cross-link was short lived in both DNA compartments, with a half-life of 4.5 and 3.3 h in the DHFR gene and mtDNA respectively. The kinetics of total Adriamycin adduct formation, detected using [14C]Adriamycin, was similar to that of cross-link formation. Maximal adduct levels (30 lesions/10 kb) were observed following incubation at 20 {micro}M drug for 8 h. The formation of such high levels of adducts and cross-links could therefore be expected to contribute to the mechanism of action of Adriamycin. 10.1093/nar/28.4.1019 IS - 4 JF - Nucl. Acids Res. EP - 1025 TI - Interstrand cross-linking by Adriamycin in nuclear and mitochondrial DNA of MCF-7 cells VL - 28 SP - 1019 KW - adriamycin KW - cross-link KW - damage KW - dna KW - doxorubicin KW - interstrand AU - Cullinane, Carleen AU - Cutts, Suzanne AU - Panousis, Con AU - Phillips, Don PY - 2000/02/15/ UR - http://dx.doi.org/10.1093/nar/28.4.1019 ER -