The relationship between serum water proton T1 and protein content in the P388 leukemic mouse and the effect of chemotherapy by cis-diamminedichloroplatinum(II).

Abstract

Proton NMR longitudinal relaxation times (T1; 10.7 MHz; 37 degrees C) were measured in the kidneys and blood serum of mice inoculated with P388 leukemia, and/or treated with the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-Pt). In parallel, serum total protein content, urea and creatinine levels were determined and protein fractions were separated electrophoretically. Serum T1 was found to be 1518 +/- 73 ms (1 SD) in control mice, 1670 +/- 69 ms in leukemic mice, and 1380 +/- 71 ms in the healthy and the leukemic cis-Pt treated mice. The T1 increase in leukemic serum and T1 decrease in the serum of cis-Pt injected mice are attributed to decreased and increased protein contents respectively. A detailed analysis in terms of electrophoretic fractions of serum proteins reveals that the serum relaxation rate 1/T1 is a multilinear function of the mass concentrations of the main serum protein fractions, explaining all serum T1 effects. This makes T1 a non-specific blood parameter. The kidney T1 was found to be 311 +/- 12 ms in normal mice and 334 +/- 20 ms in leukemic mice. A dramatic T1 increase is observed when the mice are injected with cis-Pt; the values are 400 +/- 38 ms and 407 +/- 39 ms for healthy and leukemic mice, respectively. This effect is related to the nephrotoxicity of the drug, as evidenced by serum urea and creatinine levels and protein content being higher than normal.