No abstract

Nuclear magnetic resonance spectroscopy has detected elevated phosphocholine levels in human tumor tissues and cells, and in cells that were transformed with the activated Ha-ras gene and stimulated in vitro with growth-promoting factors such as platelet-derived growth factor, epidermal growth factor, and phorbol ester. However, the mechanism of the elevation and the function of the increased phosphocholine levels have not been clearly demonstrated. We studied phosphocholine levels enzymatically and analyzed the activity of choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in human colon cancer and adenoma. Both choline kinase activity and phosphocholine levels were increased in colon cancer and adenoma tissue. The activation of choline kinase and the increased levels of choline kinase α α α α were partly responsible for the elevated phosphocholine levels. This study suggests that choline kinase might play a role in growth promotion or signal transduction in carcinogenesis.Key words: Choline kinase -Phosphocholine -Human colon cancerCancer of the colon is one of the most common cancers in developed countries and its prevention is of great interest throughout the world. It is thought that the accumulation of certain mutated genes, including oncogenes, tumor suppressor genes, genes for DNA-repair enzymes, and invasion/metastasis-related genes, is necessary for the onset and progression of cancer. Mutation may cause further malignant changes in cellular proliferation, especially in enzymatic properties and activity.1-3) Some of the changes in enzymatic properties and activity with proliferation may be advantageous to the cancer cells. [4][5][6][7] Studying the cellular properties of cancer cells improves our understanding of the mechanism of cellular growth control and sheds further light on cancer prevention and treatment. 8) Choline kinase is the first enzyme in the cytidine 5′-diphosphate (CDP)-choline pathway for the synthesis of phosphatidylcholine, and phosphorylates choline to phosphocholine using adenosine 5′-triphosphate (ATP) as the phosphate donor. [9][10][11] In vitro studies of oncogenic ras proteins, and products and growth factors have shown that phosphocholine contributes to cellular growth regulation and intracellular signal transduction. Ras proteins play a pivotal role in cellular signal transduction, and help regulate cellular proliferation and terminal differentiation. [12][13][14] Microinjecting the oncogenic Ha-ras gene product p21 ras into Xenopus oocytes causes meiosis, 15) quickly activates choline kinase and elevates phosphocholine levels. 16)Transforming fibroblastic cells with oncogenic Ha-ras also activates choline kinase. [17][18][19] Growth factors essential for cellular growth also activate choline kinase, elevating the intracellular phosphocholine level. Prolactin is one such growth factor for Nb 2 rat node lymphoma cells.20) It has been suggested that platelet-derived growth factor might use a choline kinase-phosphocholine route to promote c...

The thymidine stereoisotopomer, (2′S)-[2′-2 H]thymidine, which incorporates deuterium in the S configuration at the furanosyl 2′ carbon, has been synthesized and its vibrational spectra have been recorded and compared with those of normal thymidine. Infrared and Raman spectra were collected from crystalline powders, the latter using 1063-and 514.5-nm excitations; ultraviolet resonance-Raman spectra were collected from aqueous solutions using 244-nm excitation. The results show, remarkably, that virtually all normal modes of thymidine involve some degree of vibrational coupling between the thymine base residue and the deoxyribose moiety. Nevertheless, systematic assignments and correlation of the spectral frequencies of thymidine and (2′S)-[2′-2 H]thymidine have been accomplished. A finding of importance for nucleic acid structure applications is that many prominent Raman marker bands of thymidine, assigned previously as thymine ring vibrations, in fact involve appreciable coupling with the C2′ methylene group of the attached sugar. Vibrational coupling between the base and sugar groups implies frequency dependence upon sugar conformation and allows the bands in question to be exploited as markers of deoxyribose ring pucker and glycosyl orientation in Raman spectra of DNA, antiviral drugs, and other thymine-containing nucleoside analogues. The present results also enable unambiguous and novel assignment of spectral bands to specific vibrational modes of the C2′ methylene group of thymidine as follows: C2′H 2 antisymmetric stretching (2995 cm -1 ), symmetric stretching (2956 cm -1 ), scissoring (1404 cm -1 ), and wagging (1174 cm -1 ). Additionally, probable assignments are deduced for the C2′H 2 twisting (1103 cm -1 ) and rocking modes (898 cm -1 ). Normal mode assignments are also proposed for many other vibrational bands of thymidine.

HOSHIYAMA, Y., SEKINE, T. and SASABA, T. A Case-Control Study of Colorectal Cancer and Its Relation to Diet, Cigarettes, and Alcohol Consumption in Saitama Prefecture, Japan. Tohoku J. Exp. Med., 1993, 171(2), 153-165 A case-control study of colorectal cancer in relation to dietary, smoking, and drinking habits was undertaken in Saitama Prefecture, Japan. The study was based on 181 newly diagnosed cases of adenocarcinoma of the colorectum at a single institution and 653 general population controls. Dietary habits were investigated on the basis of the intake of 12 foods and 12 food groups in a food intake frequency questionnaire, together with individual food preferences. Preference for salty foods was positively related to the risk of both colon and rectal cancer, and the consumption of seaweed was inversely related to these cancers, both with a dose-response relation. Cigarette smoking was inversely related to colon cancer risk, but not to rectal cancer risk. Alcohol intake tended to be associated inversely with colon cancer, but not with rectal cancer. In the multiple logistic regression, preference for salty foods (positively) and the consumption of seaweed (inversely) were independently related to both colon and rectal cancer risks,

No abstract