| Abstract
| - Sufficient evidence has accumulated to identify DNA as the relevant pharmacological targetof antitumor cisplatin [cis-diamminedichloroplatinum(II)]. This drug is administered intravenously so thatbefore it reaches DNA in the nucleus of tumor cells it may interact with various compounds includingsulfur-containing molecules such as l-methionine or the compounds containing these residues. l-Methionineincreases the rate of reaction of cisplatin with monomeric guanosine 5‘-monophosphate, and it was suggestedon the basis of these results previously obtained by other authors that methionine residues could mediatethe transfer of platinum onto DNA. We studied in the present work the reactions of the 1:1 complexformed between cisplatin and l-methionine or N-acetyl-l-methionine with synthetic, single- and double-stranded oligodeoxyribonucleotides and natural, high molecular mass DNA by using high-pressure liquidchromatography and flameless atomic absorption spectrophotometry. The results demonstrate that bothl-methionine and N-acetyl-l-methionine decrease the rate of reaction of cisplatin with base residues innatural, high molecular mass DNA. Thus, the possibility that cisplatin bound to methionine residues servesas a drug reservoir available for platination of DNA in the nucleus of tumor cells appears unlikely.
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