Radionuclides in cigarettes may lead to carcinogenesis via p16INK4a inactivation

Journal of Environmental Radioactivity

Volumn 100, Issue 2, 2009, Pages 157-161

  Prueitt, Robyn L ^a   Goodman, Julie E ^a   Valberg, Peter A ^a  

^a GRADIENT   (United States)

Author keywords

Cigarette tobacco; Ionizing radiation; Lung cancer; Methylation; p16

Indexed keywords

CIGARETTE SMOKES; CIGARETTE SMOKING; CIGARETTE TOBACCO; EPIDEMIOLOGIC STUDIES; LUNG CANCER; P16; PROMOTER METHYLATIONS; RADIATION DOSES; RADIO-NUCLIDES; TOBACCO SMOKES; TUMOR SUPPRESSOR GENES;

ALKYLATION; BIOLOGICAL ORGANS; CARCINOGENS; IONIZING RADIATION; METHYLATION; PATHOLOGY; RADIATION; RADIATION SHIELDING; RADIOACTIVITY; RADIOISOTOPES; RADIOMETRY; RISK PERCEPTION; SMOKE; TOBACCO;

AGRICULTURAL PRODUCTS;

CANCER; EPIDEMIOLOGY; GENE EXPRESSION; HEALTH RISK; METHYLATION; OCCUPATIONAL EXPOSURE; RADIONUCLIDE; RESPIRATORY DISEASE; SMOKING; TOBACCO; TUMOR;

ANIMALS; CYCLIN-DEPENDENT KINASE INHIBITOR P16; HUMANS; LUNG NEOPLASMS; RADIOISOTOPES; SMOKING;

NICOTIANA TABACUM;

EID: 58249088687     PISSN: 0265931X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jenvrad.2008.11.008     Document Type: Review

References (43)

1. Alberg A.J., and Samet J.M. Epidemiology of lung cancer. Chest 123 (2003) 21-49
2. INK4a tumor suppressor controls p21WAF1 induction in response to ultraviolet light. Nucleic Acids Res. 35 1 (2007) 223-233
3. Andersson M., Wallin H., Jonsson M., Nielsen L.L., Visfeldt J., Vyberg M., Bennett W.P., De Benedetti V.M., Travis L.B., and Storm H.H. Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status. Int. J. Cancer 63 3 (1995) 330-336
4. INK4a in primary rat lung tumors. Mol. Cell. Biol. 17 (1997) 1366-1374
5. Belinsky S.A., Klinge D.M., Liechty K.C., March T.H., Kang T., Gilliland F.D., Sotnic N., Adamova G., Rusinova G., and Telnov V. Plutonium targets the p16 gene for inactivation by promoter hypermethylation in human lung adenocarcinoma. Carcinogenesis 25 6 (2004) 1063-1067
6. INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 11891-11896
7. Belinsky S.A., Palmisano W.A., Gilliland F.D., Crooks L.A., Divine K.K., Winters S.A., Grimes M.J., Harms H.J., Tellez C.S., Smith T.M., Moots P.P., Lechner J.F., Stidley C.A., and Crowell R.E. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res. 62 8 (2002) 2370-2377
8. Belinsky S.A. Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer. Carcinogenesis 26 9 (2005) 1481-1487
9. Centers for Disease Control (CDC). The Health Consequences of Smoking: a Report of the Surgeon General. [Internet] (2004), Centers for Disease Control (CDC), Department of Health and Human Services, Atlanta, GA. [Cited 25 July 2008]. Available from:
10. Chizhikov V., Chikina S., Gasparian A., Zborovskaya I., Steshina E., Ungiadze G., Samsonova M., Chernyaev A., Chuchalin A., and Tatosyan A. Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers. Oncogene 21 15 (2002) 2398-2405 [208-0587]
11. Cohen B.S., Eisenbud M., and Harley N.H. Alpha radioactivity in cigarette smoke. Radiat. Res. 83 1 (1980) 190-196
12. Cohen B.S., Eisenbud M., McDonald E.W., and Harley N.H. Distribution of polonium-210 in the human lung. Radiat. Res. 79 (1979) 162-168
13. 210Pb inhalation by cigarette smoking in Italy. Health Phys. 92 1 (2007) 58-63
14. Ferri E.S., and Baratta E.J. Polonium 210 in tobacco, cigarette smoke, and selected human organs. Public Health Rep. 81 2 (1966) 121-127
15. Hall P.F. Cancer risks after medical radiation. Med. Oncol. Tumor Pharmacother. 8 3 (1991) 141-145
16. Hiroyasu M., Ozeki M., Kohda H., Echizenya M., Tanaka T., Hiai H., and Toyokuni S. Specific allelic loss of p16 INK4A tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am. J. Pathol. 160 2 (2002) 419-424
17. Holtzman R.B., and Ilcewicz F.H. Lead-210 and polonium-210 in tissues of cigarette smokers. Science 153 3741 (1966) 1259-1260
18. Jain P.K. Epigenetics: the role of methylation in the mechanism of action of tumor suppressor genes. Ann. N. Y. Acad. Sci. 983 (2003) 71-83
19. Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S., Johnson B.E., and Skolnick M.H. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264 5157 (1994) 436-440
20. Kashiwabara K., Oyama T., Sano T., Fukuda T., and Nakajima T. Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non-small cell lung cancers. Int. J. Cancer 79 3 (1998) 215-220
21. Little J.B., Kennedy A.R., and McGandy R.B. Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210. Science 188 4189 (1975) 737-738
22. Little J.B., McGandy R.B., and Kennedy A. Interactions between polonium-210 α-radiation, benzo(a)pyrene, and 0.9% NaCl solution instillations in the induction of experimental lung cancer. Cancer Res. 38 (1978) 1929-1935
23. Little J.B., Radford E.P., McCombs H.L., and Hunt V.R. Distribution of polonium-210 in pulmonary tissues of cigarette smokers. N. Engl. J. Med. 273 25 (1965) 1343-1351
24. Marmorstein J. Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes?. South. Med. J. 79 2 (1986) 145-150
25. Martell E.A. Radioactivity of tobacco trichomes and insoluble cigarette smoke particles. Nature 249 454 (1974) 215-217
26. Martell E.A. Tobacco radioactivity and cancer in smokers. Am. Sci. 63 (1975) 404-412
27. Martell E.A. α-Radiation dose at bronchial bifurcations of smokers from indoor exposure to radon progeny. Proc. Natl. Acad. Sci. U.S.A. 80 (1983) 1285-1289
28. National Council on Radiation Protection and Measurements (NCRP). Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation (2001), National Council on Radiation Protection and Measurements (NCRP), Bethesda, MD NCRP Report No. 136
29. National Council on Radiation Protection and Measurements (NCRP). Ionizing Radiation Exposure of the Population of the United States (1987), National Council on Radiation Protection and Measurements (NCRP), Bethesda, MD NCRP Report No. 93
30. Palmisano W.A., Divine K.K., Saccomanno G., Gilliland F.D., Bayling S.B., Herman J.G., and Belinsky S.A. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res. 60 21 (2000) 5954-5958
31. Radford E.P., and Hunt V.R. Polonium-210: a volatile radioelement in cigarettes. Science 143 1603 (1964) 247-249
32. Radiation Effects Research Foundation (RERF). RERF Glossary. [Internet] (2007), Radiation Effects Research Foundation (RERF), Hiroshima, Japan. Available from:
33. INK4a/CDKN2A tumor suppressor and its relatives. Biochim. Biophys. Acta 1378 2 (1998) F115-F177
34. 2 and asbestos. Health Phys. 28 (1975) 383-386
35. 210Po in dry tobacco leaves in Greece. J. Environ. Radioact. 82 (2006) 94-102
36. Singal R., and Ginder G.D. DNA methylation. Blood 93 12 (1999) 4059-4070
37. INK4a in primary rat lung tumors. Mol. Cell. Biol. 17 (1997) 1366-1374
38. Thompson D.E., Mabuchi K., Ron E., Soda M., Tokunaga M., Ochikubo S., Sugimoto S., Ikeda T., Terasaki M., Izumi S., and Preston D.L. Cancer incidence in atomic bomb survivors. Part II: solid tumors, 1958-1987. Radiat. Res. 137 Suppl. 2 (1994) S17-S67
39. Tokarskaya Z.B., Okladnikova N.D., Belyaeva Z.D., and Drozhko E.G. The influence of radiation and nonradiation factors on the lung cancer incidence among the workers of the nuclear enterprise Mayak. Health Phys. 69 (1995) 356-366
40. Tso T.C., Harley N., and Alexander L.T. Source of lead-210 and polonium-210 in tobacco. Science 153 3738 (1966) 880-882
41. United States Environmental Protection Agency (US EPA). Radiation in Tobacco. [Internet] (2006), United States Environmental Protection Agency (US EPA), Washington, DC. [Cited 25 July 2008]. Available from:
42. Winters T.H., and DiFrenza J.R. Radioactivity and lung cancer in active and passive smokers. Chest 84 6 (1983) 653-654
43. Yuile C.L., Berke H.L., and Hull T. Lung cancer following polonium-210 inhalation in rats. Radiat. Res. 31 4 (1967) 760-774