Abstract
The ability of aqueous extracts of cigarette tar to nick DNA was investigated using viable mammalian cells. Tar extracts contain a radical with a stable electron spin resonance (ESR) signal at g = 2.0036 characteristic of a semiquinone. The association of the tar component that carries the ESR signal with DNA was demonstrated using viable rat alveolar macrophages. The formation of single-strand DNA breaks caused by cigarette tar extracts in viable rat thymocytes follows saturation kinetics, indicating a tar component associates with DNA and then nicks it. These studies support our hypothesis that tar components that contain the cigarette tar radical can enter cells, associate with, and then nick DNA.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anders M. W., Dekant W., Vamvakas S. Glutathione-dependent toxicity. Xenobiotica. 1992 Sep-Oct;22(9-10):1135–1145. doi: 10.3109/00498259209051867. [DOI] [PubMed] [Google Scholar]
- Borish E. T., Cosgrove J. P., Church D. F., Deutsch W. A., Pryor W. A. Cigarette tar causes single-strand breaks in DNA. Biochem Biophys Res Commun. 1985 Dec 17;133(2):780–786. doi: 10.1016/0006-291x(85)90972-6. [DOI] [PubMed] [Google Scholar]
- Borish E. T., Pryor W. A., Venugopal S., Deutsch W. A. DNA synthesis is blocked by cigarette tar-induced DNA single-strand breaks. Carcinogenesis. 1987 Oct;8(10):1517–1520. doi: 10.1093/carcin/8.10.1517. [DOI] [PubMed] [Google Scholar]
- Butler J., Hoey B. M. Reactions of glutathione and glutathione radicals with benzoquinones. Free Radic Biol Med. 1992;12(5):337–345. doi: 10.1016/0891-5849(92)90082-r. [DOI] [PubMed] [Google Scholar]
- Church D. F., Pryor W. A. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect. 1985 Dec;64:111–126. doi: 10.1289/ehp.8564111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cosgrove J. P., Borish E. T., Church D. F., Pryor W. A. The metal-mediated formation of hydroxyl radical by aqueous extracts of cigarette tar. Biochem Biophys Res Commun. 1985 Oct 15;132(1):390–396. doi: 10.1016/0006-291x(85)91034-4. [DOI] [PubMed] [Google Scholar]
- Davis W. B., Pacht E. R., Spatafora M., Martin W. J., 2nd Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers. J Lab Clin Med. 1988 Mar;111(3):293–298. [PubMed] [Google Scholar]
- Evans M. D., Church D. F., Pryor W. A. Aqueous cigarette tar extracts damage human alpha-1-proteinase inhibitor. Chem Biol Interact. 1991;79(2):151–164. doi: 10.1016/0009-2797(91)90079-m. [DOI] [PubMed] [Google Scholar]
- Fielding S., Short C., Davies K., Wald N., Bridges B. A., Waters R. Studies on the ability of smoke from different types of cigarettes to induce DNA single-strand breaks in cultured human cells. Mutat Res. 1989 Sep;214(1):147–151. doi: 10.1016/0027-5107(89)90208-x. [DOI] [PubMed] [Google Scholar]
- Greening A. P., Lowrie D. B. Extracellular release of hydrogen peroxide by human alveolar macrophages: the relationship to cigarette smoking and lower respiratory tract infections. Clin Sci (Lond) 1983 Dec;65(6):661–664. doi: 10.1042/cs0650661. [DOI] [PubMed] [Google Scholar]
- Hannan S. E., Harris J. O., Sheridan N. P., Patel J. M. Cigarette smoke alters plasma membrane fluidity of rat alveolar macrophages. Am Rev Respir Dis. 1989 Dec;140(6):1668–1673. doi: 10.1164/ajrccm/140.6.1668. [DOI] [PubMed] [Google Scholar]
- Hoidal J. R., Fox R. B., LeMarbe P. A., Perri R., Repine J. E. Altered oxidative metabolic responses in vitro of alveolar macrophages from asymptomatic cigarette smokers. Am Rev Respir Dis. 1981 Jan;123(1):85–89. doi: 10.1164/arrd.1981.123.1.85. [DOI] [PubMed] [Google Scholar]
- Lehnert B. E., Valdez Y. E., Holland L. M. Pulmonary macrophages: alveolar and interstitial populations. Exp Lung Res. 1985;9(3-4):177–190. doi: 10.3109/01902148509057522. [DOI] [PubMed] [Google Scholar]
- Lower E. E., Strohofer S., Baughman R. P. Bleomycin causes alveolar macrophages from cigarette smokers to release hydrogen peroxide. Am J Med Sci. 1988 Mar;295(3):193–197. doi: 10.1097/00000441-198803000-00006. [DOI] [PubMed] [Google Scholar]
- McCusker K., Hoidal J. Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. Am Rev Respir Dis. 1990 Mar;141(3):678–682. doi: 10.1164/ajrccm/141.3.678. [DOI] [PubMed] [Google Scholar]
- Murty V. S., Penning T. M. Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1,2-dione. Chem Biol Interact. 1992 Sep 28;84(2):169–188. doi: 10.1016/0009-2797(92)90077-x. [DOI] [PubMed] [Google Scholar]
- Nakayama T., Church D. F., Pryor W. A. Quantitative analysis of the hydrogen peroxide formed in aqueous cigarette tar extracts. Free Radic Biol Med. 1989;7(1):9–15. doi: 10.1016/0891-5849(89)90094-4. [DOI] [PubMed] [Google Scholar]
- Nakayama T., Kaneko M., Kodama M., Nagata C. Cigarette smoke induces DNA single-strand breaks in human cells. Nature. 1985 Apr 4;314(6010):462–464. doi: 10.1038/314462a0. [DOI] [PubMed] [Google Scholar]
- Pryor W. A. Cigarette smoke and the involvement of free radical reactions in chemical carcinogenesis. Br J Cancer Suppl. 1987 Jun;8:19–23. [PMC free article] [PubMed] [Google Scholar]
- Pryor W. A., Hales B. J., Premovic P. I., Church D. F. The radicals in cigarette tar: their nature and suggested physiological implications. Science. 1983 Apr 22;220(4595):425–427. doi: 10.1126/science.6301009. [DOI] [PubMed] [Google Scholar]
- Pryor W. A., Prier D. G., Church D. F. Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar. Environ Health Perspect. 1983 Jan;47:345–355. doi: 10.1289/ehp.8347345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pryor W. A., Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann N Y Acad Sci. 1993 May 28;686:12–28. doi: 10.1111/j.1749-6632.1993.tb39148.x. [DOI] [PubMed] [Google Scholar]
- Randerath E., Danna T. F., Randerath K. DNA damage induced by cigarette smoke condensate in vitro as assayed by 32P-postlabeling. Comparison with cigarette smoke-associated DNA adduct profiles in vivo. Mutat Res. 1992 Jul;268(1):139–153. doi: 10.1016/0027-5107(92)90091-f. [DOI] [PubMed] [Google Scholar]
- Rithidech K., Chen B. T., Mauderly J. L., Whorton E. B., Jr, Brooks A. L. Cytogenetic effects of cigarette smoke on pulmonary alveolar macrophages of the rat. Environ Mol Mutagen. 1989;14(1):27–33. doi: 10.1002/em.2850140106. [DOI] [PubMed] [Google Scholar]
- Soliman D. M., Twigg H. L., 3rd Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. 1992 Oct;263(4 Pt 1):L471–L478. doi: 10.1152/ajplung.1992.263.4.L471. [DOI] [PubMed] [Google Scholar]
- Thompson A. B., Bohling T., Heires A., Linder J., Rennard S. I. Lower respiratory tract iron burden is increased in association with cigarette smoking. J Lab Clin Med. 1991 Jun;117(6):493–499. [PubMed] [Google Scholar]