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1.
D B Clayson 《Mutation research》1985,154(3):205-217
Experimental research designed to determine the effects of variations in diet on the carcinogenic and mutagenic processes is difficult to conduct and even more difficult to interpret in terms of the likely response that such variations will have on the expression of human cancer and mutation. Although some of these difficulties may be due to a failure to persuade adequate numbers of highly trained nutritionists to enter into this type of research, a more germaine reason may be that the high level of complexity of both diet and the disease processes is such as to confound present efforts at interpretation. It is suggested that a stepwise analysis of the effects of dietary factors on each critical stage in carcinogenesis or mutagenesis may ultimately lead to results that are more easily interpreted in terms of human response. To this end it is proposed that studies of DNA-carcinogen or DNA-mutagen adduct formation, or other DNA damage, DNA replication and relevant DNA repair at the target site may be a useful guide to the effect of nutritional changes on mutation and/or cancer initiation. DNA replication at various stages of carcinogenesis, modification of hormonal levels, modification of immune response, or other factors as influenced by diet may provide markers for cancer development. The integration of this data to give an overall perception of the effects of nutrition is briefly discussed. 相似文献
2.
Purification of the gam gene-product of bacteriophage Mu and determination of the nucleotide sequence of the gam gene. 总被引:1,自引:0,他引:1 下载免费PDF全文
The gam gene of bacteriophage Mu encodes a protein which protects linear double stranded DNA from exonuclease degradation in vitro and in vivo. We purified the Mu gam gene product to apparent homogeneity from cells in which it is over-produced from a plasmid clone. The purified protein is a dimer of identical subunits of 18.9 kd. It can aggregate DNA into large, rapidly sedimenting complexes and is a potent exonuclease inhibitor when bound to DNA. The N-terminal amino acid sequence of the purified protein was determined by automated degradation and the nucleotide sequence of the Mu gam gene is presented to accurately map its position in the Mu genome. 相似文献
3.
We have evaluated codon usage bias in Drosophila histone genes and have
obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat
unit. This repeat contains genes for all five histone proteins (H1, H2a,
H2b, H3, and H4) and differs from the previously reported one by a second
EcoRI site. These D. hydei repeats have been aligned to each other and to
the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from
D. melanogaster. In each species, base composition at synonymous sites is
similar to the average genomic composition and approaches that in the small
intergenic spacers of the histone gene repeats. Accumulation of synonymous
changes at synonymous sites after the species diverged is quite high. Both
of these features are consistent with the relatively low codon usage bias
observed in these genes when compared with other Drosophila genes. Thus,
the generalization that abundantly expressed genes in Drosophila have high
codon bias and low rates of silent substitution does not hold for the
histone genes.
相似文献
4.
The problems that arise in the interpretation of experimental data on chemical carcinogenesis are addressed. In particular, the difficulties in demonstrating negative results are shown to present problems in delineating carcinogens from noncarcinogens. The use of the virtually safe dose estimated under the assumption of low dose linearity is shown to lead to potentially anomalous results if used indiscriminately in bioassays in which no statistically significant increase in tumor occurrence is induced. It is suggested that there is a need to establish an operational definition of negativity in carcinogenesis, with the realization that this definition may be revised in light of new information. The establishment of negativity in aligning data from positive and negative experiments and in considering possible thresholds is also discussed. 相似文献
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Clayson J Jales A Tyacke RJ Hudson AL Nutt DJ Lewis JW Husbands SM 《Bioorganic & medicinal chemistry letters》2001,11(7):939-943
Two series of delta-selective ligands related to the prototypic delta-antagonist naltrindole have been prepared and evaluated in opioid binding assays with the aim of developing new PET ligands for the delta-opioid receptor. One compound (5d) had significantly higher selectivity than naltrindole, but with substantially reduced binding affinity. For those compounds retaining similar affinity to naltrindole, those having ethyl and fluoroethyl substituents afforded the highest levels of selectivity. However, none of the compounds combined the high level of affinity and selectivity ideally suited to the development of an imaging agent. 相似文献
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Differences between the results of numerical validation studies comparing in vitro and in vivo genotoxicity tests with the rodent cancer bioassay are leading to the perception that short-term tests predict carcinogenicity only with uncertainty. Consideration of factors such as the pharmacokinetic distribution of chemicals, the systems available for metabolic activation and detoxification, the ability of the active metabolite to move from the site of production to the target DNA, and the potential for expression of the induced lesions, strongly suggests that the disparate sensitivity of the different test systems is a major reason why numerical validation is not more successful. Furthermore, genotoxicity tests should be expected to detect only a subset of carcinogens, namely genotoxic carcinogens, rather than those carcinogens that appear to act by non-genetic mechanisms. Instead of relying primarily on short-term in vitro genotoxicity tests to predict carcinogenic activity, these tests should be used in a manner that emphasizes the accurate determination of mutagenicity or clastogenicity. It must then be determined whether the mutagenic activity is further expressed as carcinogenicity in the appropriate studies using test animals. The prospects for quantitative extrapolation of in vitro or in vivo genotoxicity test results to carcinogenicity requires a much more precise understanding of the critical molecular events in both processes. 相似文献
10.
Entry of simian virus 40 is restricted to apical surfaces of polarized epithelial cells. 总被引:15,自引:0,他引:15 下载免费PDF全文
The uptake of simian virus 40 (SV40) by polarized epithelial cells was investigated by growth of cells on permeable supports and inoculation on either the apical or the basolateral surface. Binding of radiolabeled SV40 occurred on the apical but not the basolateral surfaces of permissive polarized Vero C1008 cells and nonpermissive polarized MDCK cells. When similar experiments were performed on nonpolarized Vero or CV-1 cells, virus binding occurred regardless of the direction of virus input. Electron micrographs of Vero C1008 cells infected at high multiplicities revealed virions lining the surfaces of apically infected cells, while the surfaces of basolaterally infected cells were devoid of virus particles. Analysis of the binding data revealed a single class of virus receptors (9 x 10(4) per cell) with a high affinity for SV40 (Kd = 3.76 pM) on the apical surfaces of Vero C 1008 cells. Indirect immunofluorescence studies revealed that synthesis of viral capsid proteins in Vero C1008 cells occurred only when input virions had access to the apical surface. Virus yields from apically infected Vero C1008 cells were 10(5) PFU per cell, while yields obtained from basolaterally infected cells were less than one PFU per cell. These results indicate that a specific receptor for SV40 is expressed exclusively on the apical surfaces of polarized Vero C1008 cells. 相似文献