Preclinical in vitro evaluation of hematotoxicity of the cisplatin-procaine complex DPR.
We evaluated in vitro the inhibitory effect of cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) on colony formation by granulocyte/macrophage (CFU-GM) peripheral blood progenitor cells, representing a method to quantitate the toxicity of drugs to the hematopoietic system, and human leukemic cell lines. The results were compared with those obtained exposing cells to cisplatin and carboplatin. Our data showed that while DPR had a significantly better cytotoxic activity than cisplatin and carboplatin against HL60 and K562, and than carboplatin against Molt 4 cells, it showed 12 and 43 times less inhibitory effect on CFU-GM than cisplatin and carboplatin, respectively. These results suggest that the myelosuppressive activity of DPR could be lower than that of cisplatin and carboplatin, and, furthermore, that leukemic cells represent a preferential target for its cytotoxic activity compared to normal committed hemopoietic progenitor cells. All our results speak in favor of a better therapeutic index for DPR than for the other platinum compounds considered here.
Viale
Maurizio
M
Istituto Nazionale per la Ricerca sul Cancro, Unità di Farmacologia Tossicologica, Genova. maurizio.viale@istge.it
Minetti
Silvia
S
Ottone
Massimo
M
Lerza
Roberto
R
Parodi
Brunella
B
Pannacciulli
Ivo
I
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D064420:Drug-Related Side Effects and Adverse Reactions; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology*; D011343:Procaine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C080075:cisplatin-procaine complex; D011343:Procaine; D016190:Carboplatin; D002945:Cisplatin