Cis-dichlorodiammineplatinum (II). Persistent and selective inhibition of deoxyribonucleic acid synthesis in vivo.

摘要: Abstract Cis-dichlorodiammineplatinum(II) (cis-[Pt(NH3)2Cl2]0) at 10−4 M inhibits the incorporation in vitro of thymidine-methyl-3H, uridine-5-3H, and l -leucine14C into acid-insoluble fraction Ehrlich ascites tumor cells from untreated mice only after a period ofpreincubation. Similarly, when bearing well developed tumors are given this compound intraperitoneally, subsequent assessment these isotopic precursors injected shows marked impairment all three; greatest inhibition occurs 6–12 hr injection. After depression, rates uridine -leucine return to control values or somewhat greater, while striking suppression rate thymidine persists for least 96 hr. These data were interpreted as indicative possible metabolic transformation by inorganic moiety an inactive active form, although alternate tentative explanations also proposed. It was suggested that if persistent inhibitory action on DNA synthesis is directly related chemotherapeutic efficacy agent product thereof, less frequent treatment regimen may be effective daily injections evoking fewer toxic reactions.