Jerry A. Howle, G. Gale
Oct 1, 1970
Citations
0
Influential Citations
278
Citations
Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract Cis -dichlorodiammineplatinum(II) ( cis -[Pt(NH 3 ) 2 Cl 2 ] 0 ) at 10 −4 M inhibits the incorporation in vitro of thymidine-methyl- 3 H, uridine-5- 3 H, and l -leucine 14 C into the acid-insoluble fraction of Ehrlich ascites tumor cells from untreated mice only after a period ofpreincubation. Similarly, when mice bearing well developed tumors are given this compound intraperitoneally, subsequent assessment in vitro of incorporation of these isotopic precursors into tumor cells from injected mice shows marked impairment of incorporation of all three; the greatest inhibition occurs 6–12 hr after injection. After this depression, the rates of incorporation of uridine and l -leucine return to control values or somewhat greater, while a striking suppression of the rate of incorporation of thymidine persists for at least 96 hr. These data were interpreted as indicative of a possible metabolic transformation by the cells of the inorganic moiety from an inactive to an active form, although alternate tentative explanations were also proposed. It was suggested that if the persistent inhibitory action on DNA synthesis is directly related to the chemotherapeutic efficacy of this agent or a metabolic product thereof, a less frequent treatment regimen may be as effective as daily injections while evoking fewer toxic reactions.