STRUCTURALLY DIFFERENT ANTHRACYCLINES PROVOKE DIFFERENT EFFECTS ON CELL-CYCLE AND TUMOR B-CELL DIFFERENTIATION

Previously we have detected a stimulatory effect on immunoglobulin (Ig G) synthesis when hybridoma cells were treated with doxorubicin. In or der to determine whether this is a general property of anthracycline, we have selected three analogs - doxorubicin (DOX), pirarubicin (THP-D OX) and aclarubicin (ACR) - which differ mainly in the methylation sta te of their amino sugars. Cell cycle analysis by now cytometry and dru g localization by scanning confocal microscopy were also performed. Th e results show that when cells (UN2 hybridoma B cells) were exposed to subtoxic doses of DOX or THP (with unmethylated amino sugars), a stro ng increases in IgG secretion, heavy (H) and light (L) chain synthesis and the corresponding mRNA levels were induced. Furthermore these two drugs arrested the cells in the G2/M phase of the cell cycle. In cont rast, exposure to ACR (with its methylated amino sugar) at similar sub toxic doses induced a blockade of cells in the G1 phase with no increa se of IgG synthesis, at the subtoxic doses used, all three drugs could still be detected in the nucleus as well as in the cytoplasm, as dete rmined by confocal laser microscopy. Thus, the relationship between ce ll cycle blockade, IgG stimulation and anthracycline structure is sugg ested by these results. (C) 1998 Elsevier, Paris.