Abstract:
:The question was addressed whether the risk of cancer of an individual in a heterogeneous population can be predicted on the basis of measurable biochemical and biological variables postulated to be associated with the process of chemical carcinogenesis. Using the skin tumor model with outbred male NMRI mice, the latency time for the appearance of a papilloma was used as an indicator of the individual cancer risk. Starting at 8 weeks of age, a group of 29 mice was treated twice weekly with 20 nmol of 7,12-dimethylbenz[alpha]anthracene (DMBA) applied to back skin. The individual papilloma latency time ranged from 13.5 to 25 weeks of treatment. Two weeks after the appearance of the first papilloma in each mouse, an osmotic minipump delivering 5-bromo-2'-deoxyuridine was s.c. implanted and the mouse was killed 24 hr later. Levels of DMBA-DNA adducts, of 8-hydroxy-2'-deoxyguanosine, and various measures of the kinetics of cell division were determined in the epidermis of the treated skin area. The levels of 8-hydroxy-2'-deoxyguanosine and the fraction of cells in DNA replication (labeling index for the incorporation of 5-bromo-2'-deoxyuridine) were significantly higher in those mice that showed short latency times. On the other hand, the levels of DMBA-DNA adducts were lowest in animals with short latency times. The latter finding was rather unexpected but can be explained as a consequence of the inverse correlation seen for the labeling index: with each round of cell division, the adduct concentration is reduced to 50% because the new DNA strand is free of DMBA adducts until the next treatment. Under the conditions of this bioassay, therefore, oxygen radical-related genotoxicity and the rate of cell division, rather than levels of carcinogen-DNA adducts, were found to be of predictive value as indicators of an individual cancer risk.
journal_name
Proc Natl Acad Sci U S Aauthors
Fischer WH,Lutz WKdoi
10.1073/pnas.92.13.5900subject
Has Abstractpub_date
1995-06-20 00:00:00pages
5900-4issue
13eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章abstract::Human diploid fibroblasts (HDFs) possess Ca(2+)-dependent membrane currents. These currents were suppressed in late-passage normal (senescent) HDFs and prematurely senescent HDFs derived from a subject with Werner syndrome (WS), compared with early-passage normal (young) HDFs. When young HDFs were microinjected with m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.6.2186
更新日期:1994-03-15 00:00:00
abstract::A proton NMR method is described for determining the orientation of a porphyrin within the heme pocket of a hemoprotein. The pattern of the hyperfine-shifted heme methyl resonances in low-spin ferric model compounds is demonstrated to characteristically reflect the position of a localized low-symmetry perturbation on ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.12.5755
更新日期:1978-12-01 00:00:00
abstract::In 100 primary colorectal carcinomas, we demonstrate by array comparative genomic hybridization (aCGH) that 33% show DNA copy number (DCN) loss involving PARK2, the gene encoding PARKIN, the E3 ubiquitin ligase whose deficiency is responsible for a form of autosomal recessive juvenile parkinsonism. PARK2 is located on...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1009941107
更新日期:2010-08-24 00:00:00
abstract::When histones in chromatin core particles were crosslinked with dimethylsuberimidate, the resulting particles had properties closely similar to those of native core particles. A crosslinked octameric histone complex was isolated from these particles under nondenaturing conditions. Upon reaction with DNA, this octameri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.7.2780
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abstract::Glands of the uterus are essential for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development, and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2014272117
更新日期:2020-09-22 00:00:00
abstract::Protocell models are used to investigate how cells might have first assembled on Earth. Some, like oil-in-water droplets, can be seemingly simple models, while able to exhibit complex and unpredictable behaviors. How such simple oil-in-water systems can come together to yield complex and life-like behaviors remains a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1711089115
更新日期:2018-01-30 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1305569110
更新日期:2013-07-02 00:00:00
abstract::The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recentl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1018878108
更新日期:2011-02-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2004-03-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1203122109
更新日期:2012-09-25 00:00:00
abstract::The human major histocompatibility complex includes approximately 14 class II HLA genes within the HLA-D region, most of which exist in multiple allelic forms. One of these genes, the DQ3.2 beta gene, accounts for the well-documented association of HLA-DR4 with insulin-dependent diabetes mellitus and is the single all...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.3.1027
更新日期:1989-02-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.8.4227
更新日期:2000-04-11 00:00:00
abstract::Vibrio cholerae is both an inhabitant of estuarine environments and the etiologic agent of the diarrheal disease cholera. Previous work has demonstrated that V. cholerae forms both an exopolysaccharide-dependent biofilm and a Ca2+-dependent biofilm. In this work, we demonstrate a role for the O-antigen polysaccharide ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2334614100
更新日期:2003-11-25 00:00:00
abstract::We have developed an efficient, versatile, and user-friendly viral engineering and expression system that is based on in planta assembly of functional viral vectors from separate pro-vector modules. With this new system, instead of supplying a plant cell with a complete viral vector as a mature viral particle, an RNA ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0400149101
更新日期:2004-05-04 00:00:00
abstract::BALB/c murine sarcoma Meth A is known to have three missense point mutations in p53. We previously reported that a nonamer peptide containing the codon 234 mutational product (designated 234CM) elicited 234CM-specific cytotoxic T cells and that immunization with 234CM in adjuvant before tumor challenge inhibited Meth ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.6.2219
更新日期:1995-03-14 00:00:00
abstract::Among the 15 extracellular domains of the mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R), domain 11 has evolved a binding site for IGF2 to negatively regulate ligand bioavailability and mammalian growth. Despite the highly evolved structural loops of the IGF2:domain 11 binding site, affinity-enh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1513023113
更新日期:2016-05-17 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.10.4731
更新日期:1992-05-15 00:00:00
abstract::The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1995-08-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2009-07-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Human cells that suffer mild DNA damage can enter a reversible state of growth arrest known as quiescence. This decision to temporarily exit the cell cycle is essential to prevent the propagation of mutations, and most cancer cells harbor defects in the underlying control system. Here we present a mechanistic mathemat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2018-03-06 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1105594108
更新日期:2011-07-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1210040109
更新日期:2012-08-21 00:00:00
abstract::In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of a network of genes encoding erythropoietin, vascular endothelial growth factor, and several glycolytic enzymes. HIF-1 consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim) proteins, HIF-1alpha and ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.94.11.5667
更新日期:1997-05-27 00:00:00
abstract::The SOS-inducible ruvA and ruvB gene products of Escherichia coli are required for normal levels of genetic recombination and DNA repair. In vitro, RuvA protein interacts specifically with Holliday junctions and, together with RuvB (an ATPase), promotes their movement along DNA. This process, known as branch migration...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.90.4.1315
更新日期:1993-02-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2018-12-04 00:00:00
abstract::The DNA strand exchange protein RAD51 facilitates the central step in homologous recombination, a process fundamentally important for accurate repair of damaged chromosomes, restart of collapsed replication forks, and telomere maintenance. The active form of RAD51 is a nucleoprotein filament that assembles on single-s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1604807113
更新日期:2016-10-11 00:00:00
abstract::What drives scientists' position taking on matters where empirical answers are unavailable or contradictory? We examined the contentious debate on whether to limit experiments involving the creation of potentially pandemic pathogens. Hundreds of scientists, including Nobel laureates, have signed petitions on the debat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1613580114
更新日期:2017-06-13 00:00:00
abstract::Acetyl-CoA carboxylase 1 (ACC1) catalyzes the formation of malonyl-CoA, the C2 donor for de novo synthesis of long-chain fatty acids. We have identified 64 exons, including 7 alternatively spliced minor exons (1A, 1B, 1C, 3, 5A', 5A, and 5B) in human ACC1 gene ( approximately 330 kb). The gene is regulated by three pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1332670100
更新日期:2003-06-24 00:00:00
abstract::Climate change is increasing fire activity in the western United States, which has the potential to accelerate climate-induced shifts in vegetation communities. Wildfire can catalyze vegetation change by killing adult trees that could otherwise persist in climate conditions no longer suitable for seedling establishmen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1815107116
更新日期:2019-03-26 00:00:00