DNA adducts measuring

Culp, S. J., Warbritton, A. R., Smith, B. A., Li, E. E. Beland, F. A. (2000). DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene. Carcinogenesis, 21, 1433 0. 

Poirier MC, Beland FA. 1992. DNA adduct measurements and tumor incidence during chronic carcinogen exposure in animal models implications for DNA adduct-based human cancer risk assessment. Chem. Res. Toxicol. 5 749-55... 

Culp SJ, Gay lor DW, Sheldon WG, et al. 1996a. DNA adduct measurements in relation to small intestine and forestomach tumor incidence during the chronic feeding of coal tar or benzo(A)pyrene to mice. Polycyclic Aromat Compd 11 161-168. 

Comparison of mutations in lung and bladder cancers of smokers reveals that the same complex mixture, tobacco smoke, can induce different types of mutations in different tissues. Differences in exposure routes, tissue-specific metabolic pathways, and distribution of exposure components and their metabolites are expected to account for dissimilarities. DNA adduct measurements in various tissues following exposure to tobacco smoke or smoke condensate indicate there are shifts in the predominant tobacco smoke-derived DNA damaging agents in various organs. 

Table II. Cisplatin-DNA adducts measured by ELISA (attomol adduct/ug DNA) and AAS (femtomol adduct/ug DNA) in human tissues obtained at autopsy.

Santella, R. M. Monitoring human exposure to carcinogens by DNA adduct measurement. Cell Biol Toxicol, 4 511-6. 1988. 

Akcha, F. Hubert, F.V. Pfhol-Leszkowicz, A. 2003. Potential value of the comet assay and DNA adduct measurement in dab Limanda limanda) for assessment of in situ exposure to genotoxic compounds. Mutation Research, v.534, p.21-32. 

Helmenstine A., Uziel M., Vo-Dinh T., Measurement of DNA-adducts using surface-enhanced Raman- spectroscopy, J.Toxicol. Environ. Health 1993 40 195-202. 

Fluorescence and Heterogeneity of Adducts. The fluorescence properties of adducts can provide further insight into the heterogeneity of the adducts. Prusik et al (37) reported that there are two fluorescent components in covalent (+)-anti-BaPDE-DNA adducts. One component with a 75% amplitude, was characterized by a 8.2 ns lifetime, and the other by a 125 ns lifetime (in air-saturated solutions) with a 25% amplitude. Upon dilution of the DNA, the relative amplitude of the long-lived component was found to increase. Recent measurements by Undeman et al (10) indicate that the long-lived component is a minor one (42 ns, 6%), and that there are two other short-lived decay components (1.6 ns, 52% and 7.0 ns, 42% amplitude). ... 

A variety of methods for the measurement of such binding are discussed, including the use of radiolabeling, and immunological and fluorescence techniques. The structures of some of the DNA adducts which have been characterized to date are also described. 

The main features of this proposed mechanism are (l) the stereoselectivity of the BPDEs by the DNA during intercalative covalent binding and (2) the final orientation of the bound pyrene which may be oriented internally (intercalative covalent) or externally (outside the helix). The stereoselectivity occurs during covalent bond formation and after intercalation. Relaxation of the DNA allows the adduct to adjust to its final orientation. If the experimental measurements are assumed to be made on the DNA-adducts after the final orientation has been achieved, then the following interpretations can be made. 

A less invasive procedure that could provide a indication of DNA adduct formation is measurement in the urine of the mercaptic acid S-[2-N -guanl)ethyl]-N-acetylcysteine. Excretion of this metabolite into the urine of rats occurs in a dose-dependent, linear manner after intraperitoneal administration of 1,2-dibromoethane (Kim and Guengerich 1989). This biomarker has not been looked for to date in humans suspected to have exposure to 1,2-dibromoethane. 

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