The interactions of substituted pyrido[1,2-e]purines with oligonucleotides depend on the amphiphilic properties of their side chain.

Three pyrido[1,2-e]purines of increasing hydrophilicity have been synthesized to evaluate as anticancer agents. These drugs interact quite differently with a synthetic oligodeoxynucleotide d(CGATCG)2. [1] is very hydrophobic due to a phenyl residue in its side chain. It only shows limited interactions with the minihelix without any evidence of intercalation. [2] and [3], on the other hand, have one ([2]) or two ([3]) hydroxyl groups in their acyl chain and present rather amphiphilic properties. The result is a similar intercalation of these derivatives between C and G base pairs as revealed by intermolecular nOe, 1H and 31P chemical shift variations. Models for the intercalation of [2] are proposed using energy minimizations and molecular dynamics (MD) calculations subject to restraints from nOe connectivities. Simulations and experiments indicate weak stability and thus fast exchange of [2] in its intercalation site.

[Study by NMR of the modifications of brain lipid composition related to the tumor processes]. / Etude par RMN des modifications de la composition lipidique cérébrale liées aux processus tumoraux.

1H, 13C, 31P and 14N NMR spectroscopies were used to investigate the lipid composition of brain tumors (GL6 glioma) in rats, by comparison with controlateral hemispheres. Comparative indexes derived from NMR signal intensities were used to establish the statistical analysis. It was found that sterol metabolism and sphingolipid/glycerolipids ratio are significantly modified when a tumor is present.

Expression of immunological markers on leukemic cells before and after cryopreservation and thawing.

We have studied the effects of cryopreservation on the viability and on the expression of surface antigens of acute leukemia cells. Marrow samples were obtained at initial diagnosis from 89 patients with acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and acute lymphoid leukemia (ALL). In AML, the mean viability was greater than 90% in the types M1, M4, and M5 of the French-American-British classification, 79% in M2, and 3% in M3 types. The viability was 74% in AUL. In ALL, the viability was 95% for pre-B leukemias, but only 2% in T-cell leukemias. The expression of myeloid antigens was studied before and after freezing and thawing using three monoclonal antibodies (NHL30.5, against poorly differentiated granulocytic leukemias, VIMC6 against differentiated granulocytic leukemias and granulocytes; and UCHM1 or CRIS-6, against monocytic leukemias and monocytes). The percentage of cells stained by NHL30.5 and UCHM1 or CRIS-6 was very similar before and after cryopreservation. For VIMC6, the mean staining after cryopreservation was 60% of the initial one. In pre-B ALL, the stainings by anti common ALL antigen before and after cryopreservation were also very similar. We conclude that leukemic cryopreserved cells are suitable for immunologic studies. The recovery is, however, very low in promyelocytic AML and T-cell ALL.

Expression of CD 19 antigen on acute monoblastic leukemia cells at diagnosis and after TPA-induced differentiation.

We have previously shown that CD 19, a B-lymphoid differentiation antigen, is expressed on acute myeloid leukemia cells. In this study, the expression of CD 19 and CD 14 (a monocytic antigen) was investigated in 18 cases of acute monoblastic leukemia. The staining by anti-CD 19 antibody (SB4) ranged between 26 and 81% of the cells, and was significantly correlated with the staining by anti-CD 14. Double stainings confirmed that the antigens were expressed on the same cells. After a 48-hr culture in the presence of TPA, most cells became adherent and lost CD 19 antigen, whereas CD 14 was still expressed with only minimal changes. It is concluded that CD 19 antigen is expressed on more immature stages of monoblastic leukemias. The hypothesis that CD 19 could be an early monocytic differentiation antigen is discussed.