Meta-Tyrosine And Ortho-Tyrosine: Parallel Study Of Their Anti-Metastatic Effects And Their Effects On Normal Tissues

ARIEL RAMIRO STRAZZA; DANIELA MONTAGNA,; PAULA CHIARELLA; ROBERTO MEISS,; GRACIELA DRAN; RAÚL A. RUGGIERO

Congreso; LXI Reunión Anual De La Sociedad Argentina De Investigación Clínica (SAIC).; 2016

In a former paper, we demonstrated that serum meta-tyrosine(m-tyr) and ortho-tyrosine (o-tyr), two isomers of tyrosine absent innormal proteins, were responsible for the phenomenon of concomitanttumor resistance (CR) in which a tumor-bearing host inhibitsthe growth of secondary tumor implants. Herein we have comparedthe effects of both isomers on the growth of metastases producedby the highly metastatic LMM3 tumor in parallel with their effects onnormal organs and functions in the body. BALB/c mice bearing a s.c.LMM3 tumor for 25 days were divided in three groups that received,between 25 and 45 days, a daily i.v. injection of 33 mg/kg of m-tyr(n=7), o-tyr (n=7) or saline (n=15). A fourth group (n=10) was sacrificedat day 25 to evaluate the number of metastases at the onsetof treatment. At day 45, all treated and control mice were sacrificedand metastases counted. Number of metastases (Median [range])at day 25 was 25.0 [22-28]. At day 45 the number of metastaseswas: Control Group = 60.0 [44-100]; O-tyr Group = 29.0 [15-63] (p< 0.05); M-tyr Group = 17.3 [12-33] (p < 0.001). In parallel, threegroups of normal mice received a similar schedule of m-tyr (n=6),o-tyr (n=6) or saline (n=6) and after 21 days a sample of mice wassacrificed and different organs were investigated. Neither histologicnor cytologic alterations were detected even when some organs withhigh rate of renewal such as skin, bone marrow and small intestinewere studied. Hematologic cell populations in blood and lymphoidpopulations in lymph nodes and spleen were not altered either, asevaluated by microscopic observation and flow cytometry. Similarly,m-tyr-treated and o-tyr-treated mice did not display neither lowerhumoral and cellular immune responses nor alterations in the profileof serum glucose, transaminases, creatinine, uric acid and ureameaning that both tyrosine isomers exhibit strong anti-metastaticeffects without any apparent toxic-side effects on the organism.