SEEMINGLY DIVERSE ACTIVITIES OF BETA-ALETHINE

beta-Alethine (beta-alanyl-cysteamine disulfide) exhibits striking bio logical activities in diverse systems. At an optimum of about 10 ng/ml , beta-alethine (a) adapts murine liver cells to culture (53 colonies/ 10(6) cells versus none in controls), (b) delays aging of human IMR-90 fetal lung fibroblasts (102 population doubling levels versus 47 in c ontrols, producing 3 x 10(16) greater biomass), and (c) markedly stimu lates antibody-producing plaque-forming cells from murine splenocytes (16,875/10(6) cells versus 55/10(6) cells in controls) or human periph eral blood leukocytes (1826/10(6) cells versus 0/10(6) cells in contro ls). Early interventions with beta-alethine (1 ng/kg to 100 mu g/kg) s uccessfully treat NS-1 myeloma in a syngeneic murine tumor model (NS-1 myeloma). Although there are indications in this model that beta-alet hine is also effective when intervention is late, beta-alethine is ine ffective in an allogeneic murine melanoma model (Cloudman S-91 melanom a). It is inferred that beta-alethine enhances cellular phenotypic exp ression, function, and vitality in diverse biological systems and may treat certain types of neoplasia. Because atomic spacings between the amide moieties in beta-alethine are the same as in the differentiating agent hexamethylene-bis-acetamide and because the radioprotectors WR 2721 and WR 1065 lack only the carbonyl oxygen of the thiol form (beta -aletheine), biological activities already reported for these compound s are compared with those presented herein for beta-alethine. Although these comparisons have not been made in the same systems, the tentati ve conclusion is that the amide moieties of beta-alethine may be criti cal to its potency and lack of obvious toxicity in cell culture and an imal models.