Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 27 May 1994:
Vol. 264. no. 5163, pp. 1317 - 1319
DOI: 10.1126/science.8191284
Prev | Table of Contents | Next

Articles

Science, Vol 264, Issue 5163, 1317-1319
Copyright © 1994 by American Association for the Advancement of Science

articles

Geographic variation of p53 mutational profile in nonmalignant human liver

F Aguilar, CC Harris, T Sun, M Hollstein, and P Cerutti

Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Lausanne.

Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. The population of Qidong is exposed to high levels of aflatoxin B1 (AFB1), a fungal toxin that has been shown to induce the same mutation in cultured human HCC cells. To investigate the role of AFB1 and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB1 exposures are negligible, low and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB1 exposure, which supports the hypothesis that this toxin has a causative--and probably early--role in hepatocarcinogenesis.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa.
G. D. Kirk, E. Bah, and R. Montesano (2006)
Carcinogenesis 27, 2070-2082
   Abstract »    Full Text »    PDF »
Separate Origins of Hepatitis B Virus Surface Antigen-Negative Foci and Hepatocellular Carcinomas in Transgenic HBsAg (alb/psx) Mice.
D. R. Crawford, S. Ostrowski, D. Vakharia, Z. Ilic, and S. Sell (2006)
Am. J. Pathol. 169, 223-232
   Abstract »    Full Text »    PDF »
Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients.
P. E. Jackson, S.-Y. Kuang, J.-B. Wang, P. T. Strickland, A. Munoz, T. W. Kensler, G.-S. Qian, and J. D. Groopman (2003)
Carcinogenesis 24, 1657-1663
   Abstract »    Full Text »    PDF »
Ligation of high-melting-temperature 'clamp' sequence extends the scanning range of rare point-mutational analysis by constant denaturant capillary electrophoresis (CDCE) to most of the human genome.
A. S. Kim and W. G. Thilly (2003)
Nucleic Acids Res. 31, e97
   Abstract »    Full Text »    PDF »
Differential Impact of Telomere Dysfunction on Initiation and Progression of Hepatocellular Carcinoma.
P. A. Farazi, J. Glickman, S. Jiang, A. Yu, K. L. Rudolph, and R. A. DePinho (2003)
Cancer Res. 63, 5021-5027
   Abstract »    Full Text »    PDF »
Tobacco Smoking, Harm Reduction, and Biomarkers.
P. G. Shields (2002)
J Natl Cancer Inst 94, 1435-1444
   Abstract »    Full Text »    PDF »
Sensitivity of Electrospray Ionization Mass Spectrometry Detection of Codon 249 Mutations in the p53 Gene Compared with RFLP.
G.-S. Qian, S.-Y. Kuang, X. He, J. D. Groopman, and P. E. Jackson (2002)
Cancer Epidemiol. Biomarkers Prev. 11, 1126-1129
   Abstract »    Full Text »    PDF »
Impairment of cell cycle progression by aflatoxin B1 in human cell lines.
R. Ricordy, G. Gensabella, E. Cacci, and G. Augusti-Tocco (2002)
Mutagenesis 17, 241-249
   Abstract »    Full Text »    PDF »
Oncogenic Base Substitution Mutations in Circulating Leukocytes of Normal Individuals.
V. L. Wilson, X. Yin, B. Thompson, K. R. Wade, J. P. Watkins, Q. Wei, and W. R. Lee (2000)
Cancer Res. 60, 1830-1834
   Abstract »    Full Text »
Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia.
G. D. Kirk, A.-M. Camus-Randon, M. Mendy, J. J. Goedert, P. Merle, C. Trepo, C. Brechot, P. Hainaut, and R. Montesano (2000)
J Natl Cancer Inst 92, 148-153
   Abstract »    Full Text »    PDF »
High Frequency and Heterogeneous Distribution of p53 Mutations in Aflatoxin B1-induced Mouse Lung Tumors.
A. S. Tam, J. F. Foley, T. R. Devereux, R. R. Maronpot, and T. E. Massey (1999)
Cancer Res. 59, 3634-3640
   Abstract »    Full Text »    PDF »
The light at the end of the tunnel for chemical-specific biomarkers: daylight or headlight?.
J. D. Groopman and T. W. Kensler (1999)
Carcinogenesis 20, 1-11
   Full Text »    PDF »
Hypermutability in Carcinogenesis.
B. S. Strauss (1998)
Genetics 148, 1619-1626
   Abstract »    Full Text »    PDF »
Nucleic Acid-Based Methods for the Detection of Cancer.
D. Sidransky (1997)
Science 278, 1054-1058
   Abstract »    Full Text »
Transcriptional Repression of p53 Promoter by Hepatitis C Virus Core Protein.
R. B. Ray, R. Steele, K. Meyer, and R. Ray (1997)
J. Biol. Chem. 272, 10983-10986
   Abstract »    Full Text »    PDF »
Frequent clones of p53-mutated keratinocytes in normal human skin.
A. S. Jonason, S. Kunala, G. J. Price, R. J. Restifo, H. M. Spinelli, J. A. Persing, D. J. Leffell, R. E. Tarone, and D. E. Brash (1996)
PNAS 93, 14025-14029
   Abstract »    Full Text »    PDF »
Mechanisms of Toxicity and Carcinogenesis.
B. F. Trump (1995)
Toxicol Pathol 23, 775-827
   PDF »
Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: Oxyradical overload diseases.
S. P. Hussain, K. Raja, P. A. Amstad, M. Sawyer, L. J. Trudel, G. N. Wogan, L. J. Hofseth, P. G. Shields, T. R. Billiar, C. Trautwein, et al. (2000)
PNAS 97, 12770-12775
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)