Lindauer, Elfriede and Holler, Eggehard (1996) Cellular distribution and cellular reactivity of platinum(II) complexes. BIOCHEMICAL PHARMACOLOGY, 52 (1). pp. 7-14. ISSN 0006-2952, 1873-2968
Full text not available from this repository.Abstract
We have investigated whether or not the cellular content of reactive platinum, aside from total cellular and DNA-bound platinum, is a measure of the growth inhibitory potential of a given platinum complex. Human MCF-7 breast cancer cells, after treatment with cisplatin [cis-diamminedichloroplatinum(II)] and several 1,2-diphenylethylenediamineplatinum(II) complexes at a fixed dose of 3 mu M, were analyzed for their contents of platinum in total cells, isolated nuclei, chromosomal DNA, and the cellular pool of reactive platinum, and compared with ED(50)-values. Platinum was measured by atomic absorption. Reactive platinum was identified after its reaction with calf thymus DNA that had been added to the cells before their lysis. The amounts of platinum binding to chromosomal DNA were related to previously established ED(50)-values, and such a correlation could not be found for platinum in total cells, nuclei, and, especially, reactive platinum. The observed differences in the platinum contents of DNA were referred to variations in the rate of adduct formation rather than repair because two representative platinum complexes were indistinguishable by their effects on the chloramphenicol acetyltransferase (EC 2.3.1.28) transfection system. One of the other platinum complexes accumulated, showing an increased growth inhibition in support of this interpretation with regard to the other platinum complexes. During prolonged treatment of MCF-7 cells with the platinum(II) complexes, pools of reactive platinum were found to persist even after drug depletion in the culture medium. This suggested a hitherto unrecognized cellular storage and availability of reactive platinum.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA; cisplatin; prodrug activation; platinum metabolism; platinum DNA; reactive platinum; chemotherapy |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eggehard Holler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2023 05:09 |
| Last Modified: | 05 Jul 2023 05:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51601 |
Actions (login required)
 |
View Item |
