Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems

Summary The covalent binding of tritiated benzo(a) pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP with DNA) and the biologically most relevant system (in vivo).Presented in part at the 10th Annual Meeting of the Union of Swiss Societies of Experimental Biology, Experientia34, 925 (1978), abstract.Acknowledgment. We thank Dr G. Kistler, Institute of Anatomy, University of Zurich, for generously supplying the SIRC and VERO cell lines, and Mr P. Manser for the preparation of the granuloma pouch fibroblasts.     

Comparative studies on the covalent binding of the carcinogen benzo(a)pyrene to DNA in various model systems.

The covalent binding of tritiated benzo(a)pyrene (BP) to DNA has been determined in rat liver in vivo, in rat liver perfused in situ, after incubation of BP with liver single cells, with liver homogenate, with liver microsomes and DNA, with fibroblasts from a rat granuloma pouch, and with 2 cell lines. Liver single cells were found to be a valuable compromise between the most sensitive system (microsomal incubation of BP and DNA) and the biologically most relevant system (in vivo).     

Regulatory evolution of shavenbaby/ovo underlies multiple cases of morphological parallelism

Cases of convergent evolution that involve changes in the same developmental pathway, called parallelism, provide evidence that a limited number of developmental changes are available to evolve a particular phenotype. To our knowledge, in no case are the genetic changes underlying morphological convergence understood. However, morphological convergence is not generally assumed to imply developmental parallelism. Here we investigate a case of convergence of larval morphology in insects and show that the loss of particular trichomes, observed in one species of the Drosophila melanogaster species group, has independently evolved multiple times in the distantly related D. virilis species group. We present genetic and gene expression data showing that regulatory changes of the shavenbaby/ovo (svb/ovo) gene underlie all independent cases of this morphological convergence. Our results indicate that some developmental regulators might preferentially accumulate evolutionary changes and that morphological parallelism might therefore be more common than previously appreciated.     

Unidirectional rotation in a mechanically interlocked molecular rotor

Molecular motor proteins are ubiquitous in nature and have inspired attempts to create artificial machines that mimic their ability to produce controlled motion on the molecular level. A recent example of an artificial molecular rotor is a molecule undergoing a unidirectional 120 degrees intramolecular rotation around a single bond; another is a molecule capable of repetitive unimolecular rotation driven by multiple and successive isomerization of its central double bond. Here we show that sequential and unidirectional rotation can also be induced in mechanically interlocked assemblies comprised of one or two small rings moving around one larger ring. The small rings in these [2]- and [3]catenanes move in discrete steps between different binding sites located on the larger ring, with the movement driven by light, heat or chemical stimuli that change the relative affinity of the small rings for the different binding sites. We find that the small ring in the [2]catenane moves with high positional integrity but without control over its direction of motion, while the two rings in the [3]catenane mutually block each other's movement to ensure an overall stimuli-induced unidirectional motion around the larger ring.     

A first-generation linkage disequilibrium map of human chromosome 22

DNA sequence variants in specific genes or regions of the human genome are responsible for a variety of phenotypes such as disease risk or variable drug response. These variants can be investigated directly, or through their non-random associations with neighbouring markers (called linkage disequilibrium (LD)). Here we report measurement of LD along the complete sequence of human chromosome 22. Duplicate genotyping and analysis of 1,504 markers in Centre d'Etude du Polymorphisme Humain (CEPH) reference families at a median spacing of 15 kilobases (kb) reveals a highly variable pattern of LD along the chromosome, in which extensive regions of nearly complete LD up to 804 kb in length are interspersed with regions of little or no detectable LD. The LD patterns are replicated in a panel of unrelated UK Caucasians. There is a strong correlation between high LD and low recombination frequency in the extant genetic map, suggesting that historical and contemporary recombination rates are similar. This study demonstrates the feasibility of developing genome-wide maps of LD.