EFFECTS OF HOMO-AZA-STEROIDS ON ACUTE NONLYMPHOCYTIC LEUKEMIA-CELL PROLIFERATION IN-VITRO

Homo-aza-steroids (modified steroid molecules) in their esterified for ms have been used extensively as carrier molecules of alkylating agent s against several neoplastic malignancies in vivo and in vitro, We stu died the effects of two homo-aza-steroid carrier molecules alone, name ly 3 beta- hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic- 13, 17-lactam (compound 1) and 13 no-13,17-seco-1,3,5-estratrien-17-oi c-13,17-lactam (compound 2), on human acute non-lymphocytic leukaemia cell proliferation in vitro. We used peripheral blood samples from 27 untreated ANLL patients (eight M1, four M2, two M3, six M4, three M5a, two M5b and two M6, according to FAB criteria). Proliferative activit y was estimated by using thymidine uptake and the percentage of cells in metaphase in 24, 48 and 72 h of culture. Exposure of human leukaemi c blasts with either of the two compounds resulted in enhanced cell pr oliferation in M1, M2, M4, M6 and M5a (only by compound 2) cases, wher eas there was no significant effect in the M3 and M5b cases. Our resul ts indicate that the two compounds tested exhibit stimulatory effect o n cell proliferation, particularly in blast cells possessing a relativ ely smaller degree of differentiation (M1 and M6 cases exhibiting CD34 and CD7). Further research is needed to study the cell growth effect and the therapeutic potential of these steroid molecules in human bloo d malignancies in vitro and in vivo.