Dose-dependence and stability of cisplatin binding to tissue DNA and blood proteins in rats.
Two experiments were carried out by using atomic absorption spectroscopy on the stability and dose-dependence of cisplatin [cis-diamminedichloroplatinum (II)] binding to blood proteins and tissue DNA of male Han/Wistar rats. The dose-dependence was studied by injecting 17 rats i.p. either with cisplatin (4.4, 8.0 or 11.0 mg/kg) or 0.9% NaCl (controls). The Pt concentrations in blood proteins (plasma proteins and hemoglobin) and DNAs of different tissues (kidney, liver, lung and testis) were measured 24 h after the treatment. The binding of cisplatin to blood proteins and tissue DNAs correlated with each other and the dose. The stability was studied by treating 17 rats i.v. with 8.0 mg cisplatin/kg. The Pt concentrations in kidney, liver and lung DNA were determined 5 h, 1, 3 or 5 days after the treatment. The disappearance of Pt was faster in kidney DNA than in liver or lung DNA; in 5 days the Pt concentration in kidney DNA decreased by 63% while the Pt content in liver or lung decreased by 40%. Both of these experiments showed that the binding of cisplatin to kidney DNA exceeded the other tissue DNAs examined. Testicular DNA showed the lowest level of binding. The present animal data suggest that the platination level of blood proteins may be used as a measure of Pt concentration in tissue DNA.
Mustonen
R
R
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Takala
M
M
Leppälä
S
S
Hemminki
K
K
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic
D001798:Blood Proteins; D004247:DNA; D002945:Cisplatin