Trace metals were measured by neutron-activation analyses in purified nucleic acids and histone(s) of lymphocytes from patients with acute lymphocytic leukaemia or infectious mononucleosis and from normal donor DNA isolated from lymphocytes of a patient with infectious mononucleosis and a normal donor showed a high a high content of Cr2+, Sb2+, Fe2+, and Zn2+, whereas DNA of lymphoblasts from a patient with acute lymphocytic leukaemia had a lower content of these trace metals, but the Co2+ content was 20-fold higher than in DNA or normal donor lymphocytic cells. Total histones from leukaemic cells had higher contents of most of the trace metals except for Zn2+, which was present in lesser concentration than in histones from normal donor lymphocytic cells. Lysine-rich (F1) histones showed lower contents of Cr2+, Sb2+ and Co2+, whereas arginine-rich (F3) histones had significantly higher contents of these trace metals. These observations may be of interest in that F3 histones more effectively inhibit RNA synthesis in human lymphocytic cells than do other species of histones.

RNAs isolated from cells derived from human leukemia (CCRF-CEM), infectious mononucleosis (CCRF-RKB, SB), and a normal donor (CCRF-SLT) were resolved into 4 peaks on Sephadex G-100 columns. tRNA (4S or peak IV) showed a higher ratio of 6-methyladenosine, N2, N2-dimethylguanosine and 5-methylcytosine in RKB and SB cells as compared with CEM and SLT cells. Striking differences were observed in 7-methylguanosine; there was a 4–5-fold increase in CEM cells, and a 2-fold increase in RKB and SB, as compared with SLT cells. The total content of modified minor bases, including pseudo-uridine, showed no significant quantitative differences in the 4.6S RNA (peak III) RNA. A 3–4-fold increase was seen in the 7-methylguanosine content of 5.5S (peak II) isolated from CEM cells as compared to RKB, SB and SLT cells. 3-Methylcytosine was found only in CEM, and higher ratios of minor bases were found in 5.5S RNA isolated from CEM, as compared with SLT, RKB, and SB cells. These observations are of particular interest in view of increased excretion of methylated purines in urines of patients or animals with cancer, and may reflect increased methylation reactions and/or increased metabolic turnover of methylated bases in the tumor-bearing host.

Purified chromatin isolated from lymphocytic cells derived from patients with acute leukemia, or other lymphoproliferative disorders has been compared with chromatin isolated from normal human lymphocytic cells by gel electrophoresis and differential gradient ultracentrifugation. Thermal denaturation studies showed higher Tm values for chromatin from leukemic cells, as compared to that of lymphocytic cells from normal donors or patients with infectious mononucleosis, reflecting the diverse complexity of these chromatins with respect to their varying chemical compositions. There are significant differences in the ratios of DNA:RNA:protein, as well as in the ratios of chromatin-associated histone and non-histone proteins; although chromatin-associated histones were more homogeneous than were the non-histone proteins, as adjudged by amino acid analyses and acrylamide gel electrophoresis. These differences in chromatin structure may relate to the differences in gene expression characteristic of these lymphocytic cells. The chromosomal acidic proteins isolated from the purified chromatin of human leukemic cells greatly stimulated the template activity of the chromatin in in vitro RNA synthesis. The non-histone proteins selectively interact with chromatins and influence the RNA polymerase reactions, indicating that there is selective tissue specificity of non-histone proteins.

Utilizing staining with alkaline fast green (pH 8.1) and toluidine blue O (pH 9.0) stains, the nuclear basic and acidic protein content of individual human lymphocytic cells has been quantitated cytochemically with high resolution, rapid scanning instruments. There were distinct differences in the distribution patterns of the acidic and basic proteins in these human lymphocytic cells. Nucleoli were densely stained by toluidine blue O, confirming the presence of acidic proteins. The acidic nuclear proteins:DNA and basic nuclear proteins:DNA ratios are consistent and quantitatively similar, irrespective of the diagnostic category from which the cells derived and there was a definite correlation between nuclear proteins and DNA content. However, the acidic nuclear proteins represented a larger proportion of the total dry mass of the cell than did the basic nuclear proteins, an observation which may prove to be of interest with respect to control mechanisms.

The enzyme(s) RNA‐dependent DNA polymerase (reverse transcriptase) has been isolated from human lymphocytic cell lines which have been derived from patients with leukemia, infectious mononucleosis, and from normal healthy donors. The reverse transcriptase was purified through high‐speed glycerol gradients, and by DEAE‐cellulose and phosphocellulose column chromatography. The enzyme isolated from the cultured human lymphocytes had identical chromatographic patterns. The enzyme properties were studied by utilizing synthetic templates. These synthetic templates are known to discriminate between reverse transcriptase activity and that from other cellular polymerases. The activity of reverse transcriptase from human leukemic cells was much greater than that of the enzyme isolated from cells of normal or infectious mononucleosis origin. The reverse transcriptase isolated from human leukemic cells preferred oligo(dT) · poly(dA) over templates oligo(dT) · poly(dA) and oligo(dG) · poly(rC), wherease templates oligo(dT) · poly(dA) and oligo(dG) · poly(rC) were found to be active with the enzyme isolated from normal cells. The detection of the enzyme(s) reverse transcriptase in well‐established cell lines of normal and malignant origin and its possible relation to cellular metabolism is discussed.

Bleomycin-treated mouse L-929 fibroblasts are large in size and often appear multinucleated. Quantitative cytochemical studies show that these cells have an increased content of DNA and total proteins (dry mass) per cell. The increased accumulation of DNA and protein content (4–8C or more) is compatible with and may well be related to the bleomycin-induced inhibition of cell division and the resulting endoreduplication.

RNA biosynthesis in the presence of high concentrations of actinomycin D has been studied, utilizing human cells derived from normal healthy donors, patients with infectious mononucleosis and acute lymphatic leukemia. Actinomycin D-resistant RNA synthesis ranged from 18–38, with a higher percentage in human leukemic (CCRF-CEM; CCRF-HSB) cells, as compared with normal (CCRF-EFB; CCRF-TOH) human lymphocytic cells. The RNA synthesized in the presence of actinomycin D was resistant to ribonuclease (A and T1); and greater resistance was observed in human leukemic cells as compared to the other lymphocytic cells studied herein.

AbstractDie Epoxide (I) reagieren in Gegenwart von Alkali mit Malonester (II) zu den bicyclischen Lactonen (III), die zu den Mannichprodukten (IV) umgesetzt werden.

Intact exogenous human leukemie DNA derived from cells in culture was taken up by both normal and leukemic recipient human cells, wherein it migrates to the nucleus and becomes associated with host genome. Uptake of exogenous DNA averages about 15–20 percent and was relatively higher in leukemic than in normal cells in a given culture medium.

Human (pituitary) growth hormone of known primary structure exerts a stimulatory effect(s) on experimentally growing human leukemic lumphoblasts in culture, as reflected by temporary increases in DNA, RNA, and protein synthesis. This observation may provide for development of an in vitro bioassay for human growth hormone.