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Seemingly Diverse Activities of ß-Alethine¹

School of Medicine [G. D. K., K. H. L., T. J. S.], and College of Pharmacy [P. L. M.], University of New Mexico, Albuquerque, New Mexico 87131

ß-Alethine (ß-alanyl-cysteamine disulfide) exhibits striking biological activities in diverse systems. At an optimum of about 10 ng/ml, ß-alethine (a) adapts murine liver cells to culture (53 colonies/10⁶ cells versus none in controls), (b) delays aging of human IMR-90 fetal lung fibroblasts (102 population doubling levels versus 47 in controls, producing 3 x 10¹⁶ greater biomass), and (c) markedly stimulates antibody-producing plaque-forming cells from murine splenocytes (16,875/10⁶ cells versus 55/10⁶ cells in controls) or human peripheral blood leukocytes (1826/10⁶ cells versus 0/10⁶ cells in controls). Early interventions with ß-alethine (1 ng/kg to 100 µg/kg) successfully treat NS-1 myeloma in a syngeneic murine tumor model (NS-1 myeloma). Although there are indications in this model that ß-alethine is also effective when intervention is late, ß-alethine is ineffective in an allogeneic murine melanoma model (Cloudman S-91 melanoma). It is inferred that ß-alethine enhances cellular phenotypic expression, function, and vitality in diverse biological systems and may treat certain types of neoplasia. Because atomic spacings between the amide moieties in ß-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 (ß-aletheine), biological activities already reported for these compounds are compared with those presented herein for ß-alethine. Although these comparisons have not been made in the same systems, the tentative conclusion is that the amide moieties of ß-alethine may be critical to its potency and lack of obvious toxicity in cell culture and animal models.

¹ Early work on this project was funded by NIH Grants HL16796, AM10628, and Basic Research Support Grant BRSG SO7RR-05583-25.

² To whom requests for reprints should be addressed, at University of New Mexico, P.O. Box 702, Basic Sciences Building 1, Albuquerque, NM 87131.

Received 2/15/94. Accepted 8/26/94.