Factors Influencing the Formation and Persistence of Platinum-DNA Adducts in Tissues of Rats Treated with Cisplatin
The importance of cisplatin as a cancer chemotherapeutic agent has become increasingly obvious during the past 10–15 years. Studies of the mechanism of action of this compound predate clinical studies and established very early that the antitumor effect of cisPt was due to its ability to inhibit DNA synthesis. Further studies established the probability that DNA inhibition was caused by formation of a bidentate link between the de-chlorinated cisPt molecule and nucleophilic sites on the DNA strand, likely to be either N7 or 06 of the guanine base. Recent studies by several groups (1–3) have shown that the platinum-DNA linkage is predominantly between two guanine bases (G-G) and between adenine and guanine (A-G) on the same DNA strand (intrastrand cross link) and these intrastrand links correlate closely with antitumor efficacy and DNA inhibition.
KeywordsAdduct Formation Adduct Level Guanine Base Total Platinum Male Kidney
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