thymidine-glycol and Lung-Neoplasms

Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Ascorbic Acid; Biomarkers; Carotenoids; Dehydroascorbic Acid; Deoxyguanosine; F2-Isoprostanes; Humans; Lung Neoplasms; Oxidative Stress; Risk; Smoking; Thymidine; Tobacco Products; Tobacco Smoke Pollution

We previously described a sensitive assay for measuring thymine glycol in the DNA of irradiated cells. The assay combines immunorecognition of the DNA lesion with capillary electrophoresis and laser-fluorescence detection to achieve an absolute detection level in the zeptomole (10(-21) mol) range. This article describes modifications to the protocol that overcome certain technical problems seen with the original methodology. In particular, the capillary electrophoresis is carried out at pH 8.3 rather than pH 10.5. The new protocol was used to examine removal of thymine glycol from the DNA of A549 lung adenocarcinoma cells and resting lymphocytes after exposure to 2 Gy gamma rays. Both cell types displayed similar repair kinetics. Removal of thymine glycol is almost complete at 4 hours postirradiation.

Topics: Adenocarcinoma; DNA; Electrophoresis, Capillary; Fluorescent Antibody Technique; Humans; Hydrogen-Ion Concentration; Lung Neoplasms; Thymidine