| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, [A. P., M. O.], and Department of Environmental Health Sciences, The Johns Hopkins University, Baltimore, Maryland 21205 [S. L., J. G.]
In lung and liver cancers, p53 mutations are mostly G:C to T:A transversions. This type of mutation is known to be induced by benzo(a)pyrene and aflatoxin B1 which are associated with the etiology of lung and liver cancers, respectively. Using a novel assay based on DNA polymerase fingerprint analysis, we identified p53 nucleotides targeted by these carcinogens. Thirteen of 14 nucleotide residues of the p53 gene which underwent G:C to T:A mutations in lung cancers were targeted by benzo(a)pyrene. Similarly, aflatoxin B1 formed adducts at a mutational hotspot specific for liver cancer. The same nucleotide (third base of codon 249), which mutates rarely in lung cancers, was not a target for benzo(a)pyrene. These in vitro observations indicate that p53 mutational hotspots identified in different tumors are selected targets specifically for the etiologically defined environmental carcinogens.
1 This work was supported by grants from the NIH (CA 49832) and Association pour la Recherche sur le Cancer. J. D. G. is a recipient of a Research Career Development Award from the NIH.
2 To whom requests for reprints should be addressed, at MGH Cancer Center, 149 13th Street, Charlestown, MA 02129.
Received 8/26/91. Accepted 9/25/91.
This article has been cited by other articles:
|
|
 |
|
  Y. Hu, M. P. McDermott, and S. A. Ahrendt The p53 Codon 72 Proline Allele Is Associated with p53 Gene Mutations in Non-Small Cell Lung Cancer Clin. Cancer Res., April 1, 2005; 11(7): 2502 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kim, R. C. Sills, and C. D. Houle Overview of the Molecular Biology of Hepatocellular Neoplasms and Hepatoblastomas of the Mouse Liver Toxicol Pathol, January 1, 2005; 33(1): 175 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sell Mouse Models to Study the Interaction of Risk Factors for Human Liver Cancer Cancer Res., November 15, 2003; 63(22): 7553 - 7562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Jackson, S.-Y. Kuang, J.-B. Wang, P. T. Strickland, A. Munoz, T. W. Kensler, G.-S. Qian, and J. D. Groopman Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients Carcinogenesis, October 1, 2003; 24(10): 1657 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.P. Wild and P.C. Turner The toxicology of aflatoxins as a basis for public health decisions Mutagenesis, November 1, 2002; 17(6): 471 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-S. Qian, S.-Y. Kuang, X. He, J. D. Groopman, and P. E. Jackson Sensitivity of Electrospray Ionization Mass Spectrometry Detection of Codon 249 Mutations in the p53 Gene Compared with RFLP Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1126 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Smela, M. L. Hamm, P. T. Henderson, C. M. Harris, T. M. Harris, and J. M. Essigmann The aflatoxin B1 formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma PNAS, May 14, 2002; 99(10): 6655 - 6660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Stern, D. M. Umbach, M. C. Yu, S. J. London, Z.-Q. Zhang, and J. A. Taylor Hepatitis B, Aflatoxin B1, and p53 Codon 249 Mutation in Hepatocellular Carcinomas from Guangxi, People's Republic of China, and a Meta-analysis of Existing Studies Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 617 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Smela, S. S. Currier, E. A. Bailey, and J. M. Essigmann The chemistry and biology of aflatoxin B1: from mutational spectrometry to carcinogenesis Carcinogenesis, April 1, 2001; 22(4): 535 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sanchez-Cespedes, P. A. Decker, K. M. Doffek, M. Esteller, W. H. Westra, E. A. Alawi, J. G. Herman, M. J. Demeure, D. Sidransky, and S. A. Ahrendt Increased Loss of Chromosome 9p21 but not p16 Inactivation in Primary Non-Small Cell Lung Cancer from Smokers Cancer Res., March 1, 2001; 61(5): 2092 - 2096. [Abstract] [Full Text]
|
|
|
|
|
|
P. E. Jackson, G.-S. Qian, M. D. Friesen, Y.-R. Zhu, P. Lu, J.-B. Wang, Y. Wu, T. W. Kensler, B. Vogelstein, and J. D. Groopman Specific p53 Mutations Detected in Plasma and Tumors of Hepatocellular Carcinoma Patients by Electrospray Ionization Mass Spectrometry Cancer Res., January 1, 2001; 61(1): 33 - 35. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Mizobuchi, M. Furihata, H. Sonobe, Y. Ohtsuki, T. Ishikawa, H. Murakami, A. Kurabayashi, S. Ogoshi, and S. Sasaguri Association Between p53 Immunostaining and Cigarette Smoking in Squamous Cell Carcinoma of the Esophagus Jpn. J. Clin. Oncol., October 1, 2000; 30(10): 423 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Ahrendt, J. T. Chow, S. C. Yang, L. Wu, M.-J. Zhang, J. Jen, and D. Sidransky Alcohol Consumption and Cigarette Smoking Increase the Frequency of p53 Mutations in Non-Small Cell Lung Cancer Cancer Res., June 1, 2000; 60(12): 3155 - 3159. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. K. Ross, B. Said, and R. C. Shank DNA-Damaging Effects of Genotoxins in Mixture: Modulation of Covalent Binding to DNA Toxicol. Sci., February 1, 2000; 53(2): 224 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Kelloff, J. A. Crowell, V. E. Steele, R. A. Lubet, W. A. Malone, C. W. Boone, L. Kopelovich, E. T. Hawk, R. Lieberman, J. A. Lawrence, et al. Progress in Cancer Chemoprevention: Development of Diet-Derived Chemopreventive Agents J. Nutr., February 1, 2000; 130(2): 467 - 467. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. D. Kirk, A.-M. Camus-Randon, M. Mendy, J. J. Goedert, P. Merle, C. Trepo, C. Brechot, P. Hainaut, and R. Montesano Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia J Natl Cancer Inst, January 19, 2000; 92(2): 148 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Ciolino and G. C. Yeh Inhibition of Aryl Hydrocarbon-Induced Cytochrome P-450 1A1 Enzyme Activity and CYP1A1 Expression by Resveratrol Mol. Pharmacol., October 1, 1999; 56(4): 760 - 767. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Husgafvel-Pursiainen, A. Karjalainen, A. Kannio, S. Anttila, T. Partanen, A. Ojajärvi, and H. Vainio Lung Cancer and Past Occupational Exposure to Asbestos . Role of p53 and K-ras Mutations Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 667 - 674. [Abstract] [Full Text]
|
|
|
|
|
|
J. D. Groopman and T. W. Kensler The light at the end of the tunnel for chemical-specific biomarkers: daylight or headlight? Carcinogenesis, January 1, 1999; 20(1): 1 - 11. [Full Text] [PDF]
|
|
|
|
|
|
M. F. Denissenko, J. X. Chen, M.-s. Tang, and G. P. Pfeifer Cytosine methylation determines hot spots of DNA damage in the human P53 gene PNAS, April 15, 1997; 94(8): 3893 - 3898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Brennan, J. O. Boyle, W. M. Koch, S. N. Goodman, R. H. Hruban, Y. J. Eby, M. J. Couch, A. A. Forastiere, and D. Sidransky Association between Cigarette Smoking and Mutation of the p53 Gene in Squamous-Cell Carcinoma of the Head and Neck N. Engl. J. Med., March 16, 1995; 332(11): 712 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Lee, Y.-W. Ye, J. Chen, X. Li, P. G. Waber, and P. D. Nisen p53, Retinoblastoma, and Human Papillomavirus in Squamous Cell Carcinoma and Adjacent Normal Mucosa of the Upper Aerodigestive Tract Arch Otolaryngol Head Neck Surg, October 1, 1993; 119(10): 1125 - 1131. [Abstract] [PDF]
|
|
|
|
 |
|
 G. C. Yeh, P. J. Daschner, J. Lopaczynska, C. J. MacDonald, and H. P. Ciolino Modulation of Glucose-6-phosphate Dehydrogenase Activity and Expression Is Associated with Aryl Hydrocarbon Resistance in Vitro J. Biol. Chem., September 7, 2001; 276(37): 34708 - 34713. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
