Interaction of nogalamycin with chromatin

Number of available nogalamycin binding sites in Sarcoma-180 chromatin is less than that present in Sarcoma-180 DNA. Gradual removal of proteins from chromatin by salt leads to increase in available drug binding sites, without appreciable alteration in binding affinity. Histones restrict the accessibility of nogalamycin to chromosomal DNA, whereas high mobility group (HMG) proteins have no effect. Association of histone H1 with chromosomal DNA has a more marked inhibitory effect on nogalamycin binding than other types of histones. Chromosomal protein induced conformational change in DNA appears to be the main factor in determining the availability of strong binding sites.     

Preferential binding of adriamycin and nogalamycin to DNase-I hypersensitive sites of Sarcoma-180 chromatin

Binding of nogalamycin and adriamycin with Sarcoma-180 ascites tumor cell chromatin was studied by a spectrofluorometric method. There was significant reduction in the number of available drug binding sites per nucleotide when the chromatin was digested with DNase I for a period which releases only 7% of the chromosomal DNA. Results indicate preferential binding of these drugs with DNase I hypersensitive sites of chromatin. The DNase-I hypersensitive sites of chromatin were shown to correlate to the sequences required for gene expression. Further digestion with DNase I increases availability of drug binding sites, probably due to relaxation of the compact chromatin.     

Antitumour activity of some plants from Meghalaya and Mizoram against murine ascites Dalton's lymphoma

Total five plants, three from Mizoram (Dillenia pentagyna, Ageratum conyzoides, Blumea lanceolaria) and two from Meghalaya (Potentilla fulgens, Taxus baccata) were studied for their antitumour activity against murine ascites Dalton's lymphoma (DL) in vivo. Only three plants showed the different magnitude of antitumour activity. Out of these three plants, the antitumour activity was maximally observed with the methanol extract of the stem bark of D. pentagyna as compared to the aqueous extract of the roots of A. conyzoides and aqueous extract of the root of P. fulgens. An increase in glutathione levels in Dalton's lymphoma cells was observed during tumour growth. Changes in glutathione and protein levels were also investigated in the liver and Dalton's lymphoma cells of tumour-bearing mice following the treatment with the extract of D. pentagyna which showed the highest antitumour activity as compared to the other two plant extracts. Glutathione in the liver and DL cells of treated tumour-bearing mice was found to be decreased. The protein concentration in liver and DL cells decreased mainly at 96 hr of treatment. It may be concluded that the natural product of D. pentagyna promises to be more active against Dalton's lymphoma than others and the decrease in glutathione level may be one of the important steps in resulting this antitumour effect.     

Interactions between rnacrophage cytokines and eicosanoids in expression of antitumour activity

Cytokines and eicosanoid products of macrophages play an essential role in expression of antitumour activity of macrophages either in a cell-to-cell contact system between the effector and the target cell or as cell-free soluble products. In this review the relationship between three main monokines, namely TNF-alpha, IL-1 and IL-6 and the interrelationship between these monokines and eicosanoids (PGE(2), PGI(2), LTB(4), LTC(4)) in their production and in expression of antitumour activity is discussed. Emphasis is given to the effect of tumour burden on production of the monokines and of the eicosanoids and on the production of these compounds by the tumour cells. Finally, the therapeutic implications drawn from animal studies and clinical trials is discussed.     

肉瘤-180小鼠体液中抑癌因子的研究

本文报告从肉瘤-180小鼠腹水液中分离出抑癌因子,并将其与艾氏腹水瘤小鼠腹水中的抑癌因子进行比较。结果表明,二者具有相同的生物学特性和理化性质:1.它们均能杀伤不同的癌细胞株,但对正常细胞没有影响;2.经聚丙烯酰胺凝胶电泳,为泳动速率相同的均一多肽。     

The extraction by micrococcal nuclease of glucocorticoid receptors and mouse mammary tumor virus DNA sequences is dissociated.

Glucocorticoid receptors (RG) and mammary tumor virus (MM-TV) DNA sequences were extracted by micrococcal nuclease digestion from the nuclei of C3H mouse mammary tumor cells in order to specify their relative distribution in chromatin. RG was labelled and translocated into the nuclei by incubating cells with 3H Dexamethasone (3H Dex). The purified nuclei were then treated at 2 degrees C with micrococcal nuclease. Three chromatin fractions were successively obtained: an isotonic extract (ne3H1), ahypotonic extract (ne2) and the residual pellet (P). The Dex-RG complexes were measured by the hydroxyapatite technique. The MMTV DNA sequences were titrated by molecular hybridization with an excess of MMTV radioactive cDNA probe. Up to 75% of the nuclear 3H Dex and the MMTV radioactive cDNA probe. Up to 75% of the nuclear 3H Dex and MMTV DNA sequences were extracted in a concentration dependent manner while only 10-15% of nucleic acids became soluble in 10% perchloric acid. The extracted 3H Dex-RG complex was found to be partly bound to soluble chromatin and partly free. The free complex displayed similar sedimentation constants (4S, 7S) and DNA binding ability to the cytosol receptor. The 3H Dex-RG complexes were 2 to 8 fold more concentrated in ne1, which is known to be enriched in active chromatin, than in ne2. Conversely, the concentration of MMTV DNA sequences per microgram DNA was the same in the three nuclear fractions. These results suggest that the Dex-RG complexes are concentrated in an active fraction of chromatin. We propose that, among the 20-30 copies of MMTV genes per haploid genome, only a small proportion are transcribed or regulated.