Effect of cadmium on human ovarian cancer cells with acquired cisplatin resistance.
Cadmium (Cd) dichloride is a compound that has teratogenic, mutagenic, and carcinogenic properties. Recent reports have suggested the possibility that this compound may also have tumor suppressive properties in some settings. For these reasons, we have studied the subcellular pharmacological profile of elemental cadmium in human ovarian cancer cells, when administered as cadmium dichloride. The cell lines A2780 and A2780/CP70 were used, which are well characterized with respect to their cellular response to platinum-based compounds. Cd was measured in all experiments with the use of atomic absorbance spectrometry with Zeeman background correction. In both cell lines, there were direct relationships between; drug dose and cellular accumulation of drug; cellular accumulation of drug and DNA damage levels; and DNA damage levels and cytotoxicity. These cell lines differed in that the cisplatin-resistant A2780/CP70 cell line, was also comparatively resistant to cadmium dichloride. This enhanced cellular resistance appeared to be mediated through decreased drug accumulation, and increased cellular tolerance to higher levels of DNA damage. Total genomic DNA repair and cytosolic inactivation of drug appeared not to differ substantively between these two cell lines.
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892.
K B
KB
Lee
R J
RJ
Parker
E
E
Reed
D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002478:Cells, Cultured; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D004273:DNA, Neoplasm; D002104:Cadmium; D002945:Cisplatin