Benzo[a]pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice

Background: Gene expression changes induced by carcinogens may identify differences in molecular function between target and non-target organs. Target organs for benzo[a]pyrene (BaP) carcinogenicity in mice (lung, spleen and forestomach) and three non-target organs (liver, colon and glandular stomach) were investigated for DNA adducts by 32P-postlabelling, for gene expression changes by cDNA microarray and for miRNA expression changes by miRNA microarray after exposure of animals to BaP. Results: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. cDNA microarray analysis showed a variety of genes modulated significantly by BaP in the six organs and the overall gene expression patterns were tissue specific. Gene ontology analysis also revealed that BaP-induced bioactivities were tissue specific; eight genes (Tubb5, Fos, Cdh1, Cyp1a1, Apc, Myc, Ctnnb1 and Cav) showed significant expression difference between three target and three non-target organs. Additionally, several gene expression changes, such as in Trp53 activation and Stat3 activity suggested some similarities in molecular mechanisms in two target organs (lung and spleen), which were not found in the other four organs. Changes in miRNA expression were generally tissue specific, involving, in total, 21/54 miRNAs significantly up- or down-regulated. Conclusions: Altogether, these findings showed that DNA adduct levels and early gene expression changes did not fully distinguish target from non-target organs. However, mechanisms related to early changes in p53, Stat3 and Wnt/β-catenin pathways may play roles in defining BaP organotropism

An SMP Soft Classification Algorithm for Remote Sensing

This work introduces a symmetric multiprocessing (SMP) version of the continuous iterative guided spectral class rejection (CIGSCR) algorithm, a semiautomated classification algorithm for remote sensing (multispectral) images. The algorithm uses soft data clusters to produce a soft classification containing inherently more information than a comparable hard classification at an increased computational cost. Previous work suggests that similar algorithms achieve good parallel scalability, motivating the parallel algorithm development work here. Experimental results of applying parallel CIGSCR to an image with approximately 10^8 pixels and six bands demonstrate superlinear speedup. A soft two class classification is generated in just over four minutes using 32 processors

Genotoxicity: damage to DNA and its consequences

A genotoxin is a chemical or agent that can cause DNA or chromosomal damage. Such damage in a germ cell has the potential to cause a heritable altered trait (germline mutation). DNA damage in a somatic cell may result in a somatic mutation, which may lead to malignant transformation (cancer). Many in vitro and in vivo tests for genotoxicity have been developed that, with a range of endpoints, detect DNA damage or its biological consequences in prokaryotic (e.g. bacterial) or eukaryotic (e.g. mammalian, avian or yeast) cells. These assays are used to evaluate the safety of environmental chemicals and consumer products and to explore the mechanism of action of known or suspected carcinogens. Many chemical carcinogens/ mutagens undergo metabolic activation to reactive species that bind covalently to DNA, and the DNA adducts thus formed can be detected in cells and in human tissues by a variety of sensitive techniques. The detection and characterisation of DNA adducts in human tissues provides clues to the aetiology of human cancer. Characterisation of gene mutations in human tumours, in common with the known mutagenic profiles of genotoxins in experimental systems, may provide further insight into the role of environmental mutagens in human cancer

DEMAND AND SUPPLY ASSESSMENT FOR THE MICHIGAN FROZEN POTATO INDUSTRY

This report presents a general assessment of the demand and supply conditions affecting the Michigan frozen potato industry. The information has been drawn from various secondary sources and interviews with key industry informants. The report is one of the major outputs of an ongoing study being prepared for the Michigan Potato Industry Commission and funded by the Michigan Agricultural Experiment Station. This analysis was necessitated by the 80% reduction in Michigan frozen processing potato acreage by Simplot in 1997. This reduction of 5,000 acres for the Grand Rapids processing facility has created both short-term and long-term concerns for the Michigan potato industry. This assessment provides broad background information relevant to determining why this cutback occurred and its likely impact if continued in the future. The report begins with a consideration of demand conditions, including both domestic and international demand trends for consumption and consumer preferences. The report then discusses supply issues, including current North American production capacity, international sourcing trends, competition from Canadian imports, cost considerations, processing innovation, and industry consolidation. The report concludes with a section addressing key strategic issues suggested by the demand and supply trends. NOTE: This staff paper contains text only. For charts and graphs (exhibits 1-17b) which have been omitted, contact Christopher Peterson at ([email protected]).Crop Production/Industries,

Evidence for Ubiquitous Collimated Galactic-Scale Outflows along the Star-Forming Sequence at z~0.5

We present an analysis of the MgII 2796, 2803 and FeII 2586, 2600 absorption line profiles in individual spectra of 105 galaxies at 0.3<z<1.4. The galaxies, drawn from redshift surveys of the GOODS fields and the Extended Groth Strip, fully sample the range in star formation rates (SFRs) occupied by the star-forming sequence with stellar masses log M_*/M_sun > 9.5 at 0.3<z<0.7. Using the Doppler shifts of the MgII and FeII absorption lines as tracers of cool gas kinematics, we detect large-scale winds in 66+/-5% of the galaxies. HST/ACS imaging and our spectral analysis indicate that the outflow detection rate depends primarily on galaxy orientation: winds are detected in ~89% of galaxies having inclinations (i) <30 degrees (face-on), while the wind detection rate is only ~45% in objects having i>50 degrees (edge-on). Combined with the comparatively weak dependence of the wind detection rate on intrinsic galaxy properties, this suggests that biconical outflows are ubiquitous in normal, star-forming galaxies at z~0.5. We find that the wind velocity is correlated with host galaxy M_* at 3.4-sigma significance, while the equivalent width of the flow is correlated with host galaxy SFR at 3.5-sigma significance, suggesting that hosts with higher SFR may launch more material into outflows and/or generate a larger velocity spread for the absorbing clouds. Assuming that the gas is launched into dark matter halos with simple, isothermal density profiles, the wind velocities measured for the bulk of the cool material (~200-400 km/s) are sufficient to enable escape from the halo potentials only for the lowest-M_* systems in the sample. However, the outflows typically carry sufficient energy to reach distances of >50 kpc, and may therefore be a viable source of cool material for the massive circumgalactic medium observed around bright galaxies at z~0. [abridged]Comment: Submitted to ApJ. 61 pages, 25 figures, 4 tables, 4 appendices. Uses emulateapj forma

Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

<p>Abstract</p> <p>Background</p> <p>Benzo[a]pyrene (BaP) is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR) induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by ³²P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA) changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP) 1A1 and CYP1B1, which are involved in BaP metabolism.</p> <p>Results</p> <p>Following BaP exposure, cells evaded <it>G1 </it>arrest and accumulated in <it>S</it>-phase. Higher levels of DNA damage occurred in <it>S</it>- and <it>G2/M</it>- compared with <it>G0/G1-</it>enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in <it>G1</it>, the ERK pathway in <it>G1 </it>and <it>S</it>, the Nrf2 pathway in <it>S </it>and <it>G2/M </it>and the Akt pathway in <it>G2/M</it>. An important finding was that higher levels of DNA damage in <it>S- </it>and <it>G2/M</it>-enriched cultures correlated with higher levels of <it>CYP1A1 </it>and <it>CYP1B1 </it>mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE), the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle.</p> <p>Conclusions</p> <p>This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell cycle. Our results suggest that growth kinetics within a target-cell population may be important determinants of susceptibility and response to a genotoxic agent.</p