CONICET | Buscador de Institutos y Recursos Humanos

In a former paper, we demonstrated that serum meta-tyrosine (m-tyr) and ortho-tyrosine (o-tyr), two isomers of tyrosine absent in normal proteins, were responsible for the phenomenon of concomitant tumor resistance (CR) in which a tumor-bearing host inhibits the growth of secondary tumor implants. Herein we have compared the effects of both isomers on the growth of metastases produced by the highly metastatic LMM3 tumor in parallel with their effects on normal 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 33mg/kg of m-tyr (n=7), o-tyr (n=7) or saline (n=15). A fourth group (n=10) was sacrificed at day 25 to evaluate the number of metastases at the onset of treatment. At day 45, all treated and control mice were sacrificed and metastases counted. Number of metastases (Median [range]) at day 25 was 25.0 [22-28]. At day 45 the number of metastases was: 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, three groups 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 was sacrificed and different organs were investigated. Neither histologic nor cytologic alterations were detected even when some organs with high rate of renewal such as skin, bone marrow and small intestine were studied. Hematologic cell populations in blood and lymphoid populations in lymph nodes and spleen were not altered either, as evaluated by microscopic observation and flow cytometry. Similarly, m-tyr-treated and o-tyr-treated mice did not display neither lower humoral and cellular immune responses nor alterations in the profile of serum glucose, transaminases, creatinine, uric acid and urea meaning that both tyrosine isomers exhibit strong anti-metastatic effects without any apparent toxic-side effects on the organism.