Some observations on the mechanisms of blocking of nuclear staining by cisplatin.

The effect of cisplatin (cis-dichloro-diamminoplatinum II) treatment on staining of nuclei with various basic dyes and with the Feulgen reaction has been studied. Although cisplatin is reported to show negligible reaction with DNA phosphates, it hs a substantial blocking effect on staining with most dyes. Short treatment with cisplatin results in binding mainly to guanine bases of DNA, causing partial blocking of the Feulgen reaction and almost complete blocking of ethidium intercalation; binding of neutral red and crystal violet is enhanced, apparently as a result of cisplatin-induced denaturation of DNA. Very prolonged cisplatin treatment does not completely block the Feulgen reaction, indicating that reaction of cisplatin with purine bases is not complete. Since attachment of cisplatin to DNA bases is unlikely to prevent binding of most basic dyes, it is suggested that the blocking of their staining may result from steric hindrance caused by formation of DNA-protein cross-links by cisplatin. Whatever the mechanism, it is incapable of producing complete blocking of staining with certain dyes. As a practical tool, it appears that rapid and almost complete blocking of staining by cisplatin may be used as an indicator of intercalative binding of dyes to DNA.