Drugs Exp Clin Res. 2000;26(5-6):231-7.
Comparative evaluation of blood plasma and tumor tissue amino acid pool in radiation or neoadjuvant preoperative therapies of breast cancer with the antitumor drug Ukrain.
Nefyodov LI, Uglyanitsa KN, Smirnov VY, Karavay AV, Brzosko W.
Laboratory of Analytical Biochemistry, Institute of Biochemistry, National Academy of Sciences of Belarus, 50 BLK, Grodno 230017, Belarus.
This study comparatively evaluated free amino acid pool formation in patients with T1-3N0-2M0 breast cancer treated with the drug Ukrain (25 patients, i.v. 100 mg/course) in combination with preoperative radiation or neoadjuvant therapies (25 subjects, total dose 20 Gy). All the patients underwent radical mastectomy. Preoperative radiation did not essentially change the range of the blood plasma parameters studied. However, we observed decreased concentrations of blood plasma ornithine and citrulline and a reduced content of aminobutyric acid, as compared with levels on admission, which may indicate an acceleration of detoxication processes in the liver. In comparison with healthy mammary gland tissue, the tumor tissue of the patients subjected to radiation therapy showed 1.5- to twofold increased concentrations of cysteate, taurine, aspartate, glutamate, proline, glycine, alanine, valine, tyrosine and histidine, which substantiates the idea of tumor tissue being a trap for numerous energy and plastic substrates and indicates active transport of the above compounds into the tumor. The application of Ukrain had virtually no influence on concentrations of the majority of blood plasma amino acids and derivatives: the total concentration of the compounds studied as well as the essential and nonessential amino acid pools remained unchanged. As compared with healthy breast tissue, the considerably increased levels of thiol-containing amino acids, such as methionine, cystine, cysteate and taurine, in the tumor tissue of patients receiving neoadjuvant therapy with Ukrain, indicates high activity of trans-sulfuration processes in this tissue. Simultaneously, in contrast to radiation therapy, Ukrain induced a marked dose-dependent increase in the concentration of proline in breast tumor tissue. The above changes were consistent with the results of the morphological study which confirmed the emergence of numerous foci of necrosis in the tumor and indicated activation of Ukrain-induced proteolytic and degradation processes in the tumor. The results obtained have led us to conclude that a mechanism of Ukrain's cancerostatic effect is to control the transport and reactions of intermediate amino acid metabolism as well as to activate proline biosynthesis in the tumor, causing enhanced development of connective tissue. It is suggested that an important practical conclusion from the present study is the lack of damaging effect of preoperative radiation therapy in the above regimen and the favorable (normalizing) action of Ukrain, at a course dose of 100 mg, on the amino acid pool formation in the organism of patients with breast cancer.