DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells.
BACKGROUND
The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics.


METHODS
DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA) hydrolysis assay.


RESULTS
While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin). In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692), or did not exist for gemcitabine.


CONCLUSIONS
The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.
Unger
Florian T
FT
Institute for Biology and Environmental Sciences, Faculty V, University of Oldenburg, Oldenburg, Germany. florian.unger@uni-oldenburg.de
Klasen
Hermann A
HA
Tchartchian
Garri
G
de Wilde
Rudy L
RL
Witte
Irene
I
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016190:Carboplatin / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016190:Carboplatin