Adenosine induces growth-cone turning of sensory neurons

The formation of appropriate connections between neurons and their specific targets is an essential step during development and repair of the nervous system. Growth cones are located at the leading edges of the growing neurites and respond to environmental cues in order to be guided to their final targets. Directional information can be coded by concentration gradients of substrate-bound or diffusible-guidance molecules. Here we show that concentration gradients of adenosine stimulate growth cones of sensory neurons (dorsal root ganglia) from chicken embryos to turn towards the adenosine source. This response is mediated by adenosine receptors. The subsequent signal transduction process involves cAMP. It may be speculated that the in vivo function of this response is concerned with the formation or the repair and regeneration of the peripheral nervous system

Cancer: evolutionary, genetic and epigenetic aspects

There exist two paradigms about the nature of cancer. According to the generally accepted one, cancer is a by-product of design limitations of a multi-cellular organism (Greaves, Nat Rev Cancer 7:213–221, 2007). The essence of the second resides in the question “Does cancer kill the individual and save the species?” (Sommer, Hum Mutat 3:166–169, 1994). Recent data on genetic and epigenetic mechanisms of cell transformation summarized in this review support the latter point of view, namely that carcinogenesis is an evolutionary conserved phenomenon—a programmed death of an organism. It is assumed that cancer possesses an important function of altruistic nature: as a mediator of negative selection, it serves to preserve integrity of species gene pool and to mediate its evolutionary adjustment. Cancer fulfills its task due apparently to specific killer function, understanding mechanism of which may suggest new therapeutic strategy

Reactivity of DNA and cis-Diamminedichloroplatinumul(II) in the Presence of Intercalating Agents

International audienceThe antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) is assumed to exhibit its toxicity by reacting with cellular DNA. Lesions produced in DNA have been characterized as bifunctional adducts including mainly intrastrand and interstrand cross-links. It is not yet known which lesion(s) is(are) responsible for selective destruction of tumor cells1–3. Drugs known to bind to DNA such as doxorubicin or bleomycin are commonly used therapeutically in combination with cis-DDP4. In vitro several studies have shown the mutual influence of cis-DDP and drugs binding to DNA5–11. One purpose of our work is to better understand how the binding of cis-DDP can be altered by the presence of other drugs interacting also with DNA. In this paper, we first show that RNA polymerases are a convenient tool to detect the adducts formed in the in vitro reaction between DNA and cis-DDP. In particular, we find that the interstrand adducts are formed at the d(GC) sites. Then, we show that a new kind of adduct, a DNA-monocoordinated complex, is formed when the reaction of platination is done in the presence of some intercalating agents. In this reaction, the DNA double helix first favors the formation of the new adduct and then favors the release of a platinum derivative. These results are discussed in relation with a catalytic activity of the DNA double helix