No abstract

The decays of 64Cu incorporated in human malignant (A549) or monkey nonmalignant (CVI) cells lead to cell death. When plotted as a function of the radioactivity introduced in the growth medium (microCi/ml at t = 0), the residual colony-forming capability decreases exponentially. The slope of the corresponding curve is steeper for A549 than for CV1 cells. Different data show that the cellular lethal event is a consequence of 64Cu transmutation and not of the irradiation by the simultaneously emitted beta- and beta+ particles. Liquid holding results show that the lethal event is irreparable. The decays of 67Cu, another radioisotope of copper, lead to cell death with the same exponential survival curve and the same lethal efficiency as for 64Cu, in spite of their different decay schemes. The lethal efficiency of both copper isotopes is close to that of 125I utilized in the form of iododeoxyuridine under the same experimental conditions as 64Cu and 67Cu. The high lethal efficiency of radioactive copper transmutations raises questions about the role in DNA functioning of copper atoms known to be present in trace amounts in this macromolecule. The lethal consequence of radioactive copper transmutations suggests that the copper atoms bound to DNA are essential for cellular functioning.

No abstract

No abstract

The possible relevance of changes in amounts of highly repetitive DNA sequences for plant differentiation and dedifferentiation processes has been suggested in several cases. Data are lacking however on 1) the genetic control of these phenomena and 2) cause-effect relationships between DNA amplification and specific ontogenetic patterns.The present study was carried out on a Nicotiana genetic system consisting of the tumorous amphidiploid N glauca x N langsdorffii, a nontumorous mutant of it, their F,, and a backcross to the tumorous parent. Backcross segregation ratios were shown to be compatible with a "single gene" hypothesis, the F, plant being nontumorous but showing a low percentage of tumors induced by wounds, 6-azauracil or X-rays.In vitro studies of excised pith tissue grown on Linsmaier and Skoog medium for different periods of time showed the presence, confirmed by cytological analyses, of amplification of highly repetitive sequences only in the nontumorous stock, as judged by reassociation experiments in the first 24-96 hours of culture. CsCl analytical ultracentrifugation of those sequences showed the appearance in the same stock of a heavy DNA satellite (density = 1.721 g d m l ) , whose presence was also confirmed by derivative melting curves. Amplification seemed to be essential for the initiation of cell division, which was completely inhibited in the nontumorous genotype and partially influenced in the F, by incorporation during the critical period (24-96 hours of the primary explant) of 5-bromo-2'-deoxy-uridine.The results are discussed in terms of an hypothesis of an integrated gene-controlled, hormone-mediated regulatory system of cell proliferation involving changes in target repetitive DNA sequences.

Experimental data on the content in metal ions of DNA preparations from various neoplastic and healthy tissues are summarized: metal ions are preferentially bound to reiterative DNA sequences, where they may induce conformational variations and thus modify the binding of effector molecules such as repressors and polymerases.A model is described where essential and toxic metals are successively loaded on ligand acceptor groups of increasing affinity and thus may reach the final active sites: enzymes and reiterative DNA sequences (equated at least partially to regulative DNA sequences). The effects of some molecules, including peptides, antibiotics, growth factors, hormones, and antineoplastic substances, on DNA conformation could be explained in part by their chelating ability.The neoplastic state may be induced by a modification of metal ion transfer chains: quantitatively by a continuous derepression of genes coding for metal ligands, genes that are only temporarily derepressed during development in normal cells, and qualitatively by modifications of the nucleotidic sequence of structural genes leading to an increase of the chelating ability of the coded metal ligand.

Macronuclear deoxyribonucleic acid (DNA) in hypotrichous ciliates consists of a set of linear molecules ranging in size from 0.5 to several tens of kilobases and typically carrying a single gene. Each minichromosome is present at a ploidy of >or=1,000 per macronucleus. These molecules are known as gene-sized molecules. Multigene molecules are also present, but are still poorly described. In analyzing the encystment-excystment cycle of Sterkiella histriomuscorum, we have characterized a set of 21 macronuclear molecules both at the DNA and complementary DNA (cDNA) levels. On a total of 23 validated coding sequences, we mapped the 5' and 3' untranslated regions for a subset of 10 and 18 transcripts, respectively. A combination of DNA and cDNA data allows us to precisely determine several structural features of macronuclear chromosomes, such as the organization of multigene molecules, an intron content higher than expected, and a conserved sequence surrounding the initiation transcription site. It also reveals one coding sequence containing a transcribed 10-bp element that displays the characteristic features of internal eliminated sequences (IES). Its presence in a fraction of the minichromosomes carrying this gene raises the possibility of an incomplete IES excision process during the development of the S. histriomuscorum macronucleus.

No abstract