Discrepancy between cytotoxicity, platinum accumulation, and DNA platination in MCF-7 breast cancer cells treated with diaqua (1,2-diphenylethylenediamine) platinum (II) sulfates and cisplatin.
Cisplatin (cis), raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine] platinum(II) sulfate (r-4F-PtSO4), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfate (m-4F-PtSO4), and meso-diaqua[1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] platinum(II) sulfate (m-2,6Cl2-4OH-PtSO4) were compared with regard to their growth inhibitory effect on MCF-7 breast cancer cells. At concentrations of 5 microM, cis, r-4F-PtSO4, and m-4F-PtSO4 were essentially equiactive, whereas m-2,6Cl2-4OH-PtSO4 was ineffective. Platinum measurements by neutron activation analysis showed that a 24-h treatment of the MCF-7 cells with r-4F-PtSO4 and m-4F-PtSO4 caused a 22.3- and 10.3-fold accumulation, respectively, whereas the accumulation factors for cis (2.55) and m-2,6Cl2-4OH-PtSO4 (1.83) were very low. The comparison of DNA-associated platinum revealed a similar tendency. After 24 h of drug exposure, the base pair/ platinum ratios were: 2.1.10(4) for r-4F-PtSO4, 3.7.10(4) for m-4F-PtSO4, 6.1.10(4) for cisplatin, and 8.1. 10(4) for m-2,6Cl2-4OH-PtSO4. Thus, the grade of cytotoxicity was correlated neither with the extent of cellular platinum enrichment nor with the degree of genomic DNA platination.
Lux
F
F
Institut für Radiochemie der Technischen Universität München, Garching, Germany.
Hollstein
M
M
Reile
H
H
Bernhardt
G
G
Schönenberger
H
H
D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts; D006801:Humans; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D002945:Cisplatin