Reaction of O6-methylguanosine with nitrite in the presence of carboxylic acid: synthesis of the purin-2-yl carboxylate

O6-Methylguanosine derivative was treated with sodium nitrite or isoamylnitrite in the presence of carboxylic acid to give the purin-2-yl carboxylate, an unusual product bearing a carboxylic group at the 2-position of the purine moiety.     

Detection of N-nitroso-bile acids at 285 nm in reverse-phase HPLC

In the present study, we developed a novel, simple, and specific detection method using an RP-HPLC at UV 285 nm for the separation and quantification of N-nitroso-bile acids. First, we found that N-nitroso-bile acids have a specific spectrophotometric absorbance at 285 nm. Using this 285 nm detection system, we could especially measure N-nitroso-bile acids, even in co-existence of non-N-nitroso-bile acids. Next, we observed the decomposition of N-nitroso-glychocholate under alkaline, acidic, and neutral conditions. N-nitroso-glychocholate rapidly decomposed under alkaline conditions (pH 9) (t(1/2) = 0.96 h), but remained fairly stable under acidic (pH 2) (t(1/2) = 12.8 h) and neutral (pH 7) (t(1/2) = 7.8 h) conditions. This study is the first report, which simply and specifically analyzes N-nitroso-bile acids using an RP-HPLC system.     

The use of Raman spectroscopy to provide an estimation of the gross biochemistry associated with urological pathologies

Near-infrared Raman spectroscopy, an optical technique that is able to interrogate biological tissues, has been used to study bladder and prostate tissues, with the objective being to provide a first approximation of gross biochemical changes associated with the process of carcinogenesis. Prostate samples for this study were obtained by taking a chip at TURP, and bladder samples from a biopsy taken at TURBT and TURP, following ethical approval. Spectra were taken from purchased biochemical constituents and different pathologies within the bladder and the prostate. We were then able to determine the biochemical basis for these pathologies by utilising an ordinary least-squares fit. We have shown for the first time that we are able to utilise Raman spectroscopy in determining the biochemical basis for the different pathologies within the bladder and prostate gland. In this way we can achieve a better understanding of disease processes such as carcinogenesis. This could have major implications in the future of the diagnosis of disease within the bladder and the prostate gland.     

The death-mutation model of carcinogenesis

Multistage models of carcinogenesis that include death and mutation of target cells at risk for cancer, but do not include cell division, may be appropriate for cancers in which clonal expansion arises downstream of the rate-determining step toward carcinogenesis. Such models are simpler than clonal expansion models, so when they are appropriate, they should be used. The purpose of this paper is to illustrate how linear systems theory applies to these death-mutation models of carcinogenesis.     

Proteome profiling of keratinocytes transforming to malignancy

To shed light on the multistep process of squamous cell carcinoma development and the underlying pathologic mechanisms, we performed comparative proteome analysis of keratinocytes, keratinocytes stimulated with Il‐1beta, and A431 epidermoid carcinoma cells. Fractionation of the cells into supernatant, nucleus, and cytoplasm was followed by protein separation, proteolytic digest, and nano‐LC separation, and fragmentation using an ion trap mass spectrometer. Specific bioinformatics tools were used to generate a list of keratinocyte‐specific proteins. Ninety percent of these proteins were found to be upregulated in keratinocytes versus the A431 cells. Classification of the identified proteins by biologic function and gene set enrichment analysis revealed that keratinocytes produced more proteins involved in cell differentiation, cell adhesion, cell junction, calcium ion, calmodulin binding, cytoskeleton organization, and cytokinesis, whereas A431 produced more proteins involved in cell cycle checkpoint, cell cycle process, RNA processing and transport, DNA damage and repair, RNA and DNA binding, and chromatin remodeling. The protein signatures of A431 and normal keratinocytes treated with IL‐1beta showed marked similarity, confirming that inflammation is an important step in malignant transformation in nonmelanoma skin cancer. Thus, proteome profiling and bioinformatic processing may support the understanding of the underlying mechanisms, with the potential to facilitate development of early biomarkers and patient‐tailored therapy.     

Optimal schedules of cancer surveillance and tumor size at detection

The paper explores methodological and mathematical aspects of a new approach to constructing optimal schedules of cancer screening. This approach consists of systematic use of tumor size at detection, combining stochastic models of tumor latency, tumor growth and tumor detection. and employing a new biologically natural screening efficiency criterion defined as the Kantorovich distance between the tumor size at spontaneous detection in the absence of screening and the tumor size at detection when both spontaneous and screening based mechanisms are in place. An explicit formula for the efficiency functional is obtained. Sample calculations suggests that in the case of exponential tumor growth, the optimal screening schedules with a fixed number of exams have a trend to uniformity.     

化学品安全性快速评价方法

简要评述了化学品安全性的传统评价方法。详细介绍了一种快速评价化学品安全性的重要方法——诱变性测试法。该方法选用几种标准(或特定)的鼠伤寒沙门氏菌(Salmonella typhimurium)作为观察对象来研究待测化学品对菌株的诱变情况，以菌株回复突变的数目表征待测化学品的诱变性。当回复突变数目为零剂量(化学品)的2倍以上时，所测定化学品具有诱变性。具有诱变性的化学品为不安全化学品。     

Modeling and analysis of the latent period of osteosarcomas induced by incorporated Pu: The role of immune responses

This paper considers the utility of a stochastic model of carcinogenesis, proposed earlier by Yakovlev and Polig, in quantitative analysis of the incidence of radiation-induced osteosarcomas in beagels injected with various amounts of ²³⁹Pu. The original version of the model failed to provide a good fit to our experimental data. The model has been generalized by incorporating a simple mechanism of lesion elimination, which is likely to be mediated by the immune system. Two versions of the model were developed: the first version ( Model 1 ) assumed malignant cells to be a target for the immune attack, while in Model 2 initiated cells were assumed to be such a target. Model 2 was rejected by the likelihood ratio test, thereby indicating that the competing model provides a more plausible explanation of the experimental data. Since in experiments with incorporated radionuclides the dose rate varies with time, dose-rate effects cannot be observed directly, and one must rely on mathematical models. The results of our numerical experiments show that, depending on the time of observation, both the direct and the inverse dose-rate effects may manifest themselves even at a fixed total dose level.     

Biochemistry of Oxidative Stress

As a normal attribute of aerobic life, structural damage to organic compounds of a wide variety (DNA, proteins, carbohydrates and lipids) may occur as a consequence of oxidative reactions. Oxidative damage inflicted by reactive oxygen species has been called “oxidative stress”. Biological systems contain powerful enzymatic and nonenzymatic antioxidant systems, and oxidative stress denotes a shift in the prooxidant/antioxidant balance in favor of the former. Diverse biological processes such as inflammation, carcinogenesis, ageing, radiation damage and photobiological effects appear to involve reactive oxygen species. This field of research provides new perspectives in biochemical pharmacology, toxicology, radiation biochemistry as well as pathophysiology.