Abstract:
:Since CP always exists in aqueous solution as a mixture of native drug and various aqua and hydroxo species, it is conceivable that one or more of these aquated species is the main form of the drug that enters the cell. To test this hypothesis, we examined the accumulation by 2008 human ovarian carcinoma cells of CP and aquated CP in Cl-, deficient medium. After 24 h in 150 mM NaNO3, HPLC analysis indicated that 54% of the platinum in solution was accounted for by aquated species. Immediately following addition of this solution to Cl- deficient RPMI 1640 medium, the initial concentrations of the aqua and hydroxo species were calculated to be 34-2400-fold higher with pre-aquated CP than with native CP. The cellular platinum accumulation, however, was the same under both conditions and was also identical to that of native CP in normal RPMI. To confirm that aquated species were actually entering the cell, the amount of platinum reaching the DNA was determined. The total platinum levels on DNA were 1.9-fold higher when cells were exposed to pre-aquated CP in Cl- deficient medium compared to CP in regular medium. We conclude that 2008 cells do not preferentially transport an aquated form of CP under these conditions compared to native CP.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Jennerwein M,Andrews PAdoi
10.1016/0304-3835(94)90205-4subject
Has Abstractpub_date
1994-06-30 00:00:00pages
215-20issue
2eissn
0304-3835issn
1872-7980pii
0304-3835(94)90205-4journal_volume
81pub_type
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