COMPARISON OF THE LEVELS OF INOSITOL METABOLITES IN TRANSFORMED HEMATOPOIETIC-CELLS AND THEIR NORMAL COUNTERPARTS

We have compared the levels of inositol metabolites in three pairs of normal and transformed cells which have been matched with respect to their cell lineage, differentiation and proliferation status: (i) normal human myeloid blast cells and the human promyelocytic leukaemic cell line, HL60; (ii) human umbilical-cord T-helper cells and C8166 cells, a HTLV1-transformed T-helper cell line; and (iii) an interleukin 3-dependent long-term culture of murine pro-B-cells (BAF3) and BAF3 cells transformed by transfection with the bcr-abl oncogene. Complex patterns of inositol metabolites were present in each of the cell populations. Although there were a number of differences in the levels of certain inositol metabolites between individual cell populations in the paired groups, we did not observe any consistent difference in the levels of inositol metabolites between the proliferating normal and transformed cells. In particular, our data do not support the reported correlation between elevated glycerophosphoinositol (GroPIns) levels and transformation of cells by membrane and cytoplasmic oncogenes which has been reported by other workers. All the cells contained high concentrations of Ins(1,3,4,5,6)P5 (between 12 and 55 muM) and InsP6 (between 37 and 105 muM). The HTLV1-transformed T-helper cells had particularly high levels of total inositol phosphates (predominantly GroPIns, an unidentified inositol bisphosphate and InsP6). The observations are discussed with reference to cell transformation and to the differentiation status of the paired populations.