Amaury G. Perez

Spontaneous Unscheduled DNA Synthesis in G1 HeLa Cells

DNA synthesis can be induced in all stages of the division cycle of mammalian cells by such agents as ultraviolet light1, X-irradiation2 and alkylating agents3. This so-called unscheduled DNA synthesis is of low magnitude compared with normal, semi-conservative DNA synthesis4, and has been equated to repair activity in damaged cells. We have observed that significant amounts of 3H-thymidine are incorporated into the DNA of HeLa cells without an extracellular stimulus, and at a time when normal, semi-conservative DNA synthesis does not occur. We report here the results of autoradiographic investigations of this spontaneous unscheduled DNA synthesis and its possible role in normal DNA metabolism.

Immunophenotypic Analysis of Lymphocytes and Myeloma Cells in Patients with Multiple Myeloma

The immunological phenotypes of lymphocytes and myeloma cells in 48 patients with multiple myeloma (MM) were analyzed using a panel of monoclonal antibodies (mAbs). Myeloma cells were positive for OKT10, BL3, PCA1 and BA2. In a few cases, they were also positive for the B cell-associated antigens J5, B1 and I2. Eight of 48 cases had more than 15% J5-positive lymphocytes, and some lymphocytes in MM expressed plasma cell-associated antigens (PCA1, BL3, OKT10), suggesting a possible clonal involvement. These observations demonstrate the heterogeneity of surface antigen expression of myeloma cells and suggest that BL3, PCA1, BA2 and J5 may be useful mAbs for purging myeloma cells from bone marrow for autologous transplantation.

Pharmacological Elimination of Tumor Cells Contaminating Normal Human Bone Marrow Using PTT-119

In this study, we evaluated the inhibitory effects of PTT-119, a new tripeptide which is known to be a bifunctional alkylating agent, on two tumor cell lines with different origins: SK-DHL-2 (B-cell diffuse histiocytic lymphoma cell line) and RPMI 8226 (Multiple myeloma patient cell line) and compared the toxicity of PTT-119 toward normal human bone marrow granulocyte macrophage (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEM) progenitors. Reduction of at least four logs was achieved on clonogenic myeloma cells after 1 hr of treatment with 25 micrograms/mL of PTT-119 either in the presence or absence of irradiated bone marrow (BM) cells. More than three and at least four logs of lymphoma cell kill were found after 1 hr of incubation with 25 and 40 micrograms/mL of the tripeptide, respectively. PTT-119 antitumor effects on SK-DHL-2 were only slightly affected in the presence of an excess of BM cells. BM cells treated for 1 hr with 25 micrograms/mL of PTT-119 showed a mean recovery of 4.5, 3.8, and 13.8% of CFU-GM, BFU-E, and CFU-GEM, respectively. The addition of 5- and 10-fold excesses of red blood cells (RBC) produced a slightly higher recovery of these hematopoietic progenitors. These results suggest that PTT-119 may be useful as a chemotherapeutic agent for the ex vivo treatment of bone marrow grafts.