Carcinogenesis, Vol. 22, No. 4, 535-545,
April 2001
© 2001 Oxford University Press
COMMENTARY |
The chemistry and biology of aflatoxin B1: from mutational spectrometry to carcinogenesis
Department of Chemistry and Division of Bioengineering and Environmental Health Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Dietary exposure to aflatoxin B1 (AFB1) is associated with an increased incidence of hepatocellular carcinoma (HCC), especially in populations in which exposure to hepatitis B virus (HBV) is a common occurrence. Most HCC samples from people living where HBV is prevalent have one striking mutational hotspot: a GC
TA transversion at the third position of codon 249 of the p53 gene. In this review, the chemical reaction of an electrophilic derivative of aflatoxin with specific DNA sequences is examined, along with the types of mutations caused by AFB1 and the sequence context dependence of those mutations. An attempt is made to assign the source of these mutations to specific chemical forms of AFB1-DNA damage. In addition, epidemiological and experimental data are examined regarding the synergistic effects of AFB1 and HBV on HCC formation and the predominance of one hotspot GCTA transversion in the p53 gene of affected individuals.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. D. Roebuck, D. N. Johnson, C. H. Sutter, P. A. Egner, P. F. Scholl, M. D. Friesen, K. J. Baumgartner, N. M. Ware, S. Bodreddigari, J. D. Groopman, et al. Transgenic Expression of Aflatoxin Aldehyde Reductase (AKR7A1) Modulates Aflatoxin B1 Metabolism but not Hepatic Carcinogenesis in the Rat Toxicol. Sci., May 1, 2009; 109(1): 41 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. C. Pang, J. W. Joh, P. J. Johnson, M. Monden, T. M. Pawlik, and R. T. P. Poon Biology of Hepatocellular Carcinoma Ann. Surg. Oncol., April 1, 2008; 15(4): 962 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. v. Brocke, H. H. Schmeiser, M. Reinbold, and M. Hollstein MEF immortalization to investigate the ins and outs of mutagenesis Carcinogenesis, November 1, 2006; 27(11): 2141 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Kirk, E. Bah, and R. Montesano Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa Carcinogenesis, October 1, 2006; 27(10): 2070 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S El-Nezami, N. N Polychronaki, J. Ma, H. Zhu, W. Ling, E. K Salminen, R. O Juvonen, S. J Salminen, T. Poussa, and H. M Mykkanen Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1199 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. U. Keller-Seitz, U. Certa, C. Sengstag, F. E. Wurgler, M. Sun, and M. Fasullo Transcriptional Response of Yeast to Aflatoxin B1: Recombinational Repair Involving RAD51 and RAD1 Mol. Biol. Cell, September 1, 2004; 15(9): 4321 - 4336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Feng, W. Hu, and M.-s. Tang Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: A possible mechanism for lipid peroxidation-induced carcinogenesis PNAS, June 8, 2004; 101(23): 8598 - 8602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. O. Alekseyev, M. L. Hamm, and J. M. Essigmann Aflatoxin B1 formamidopyrimidine adducts are preferentially repaired by the nucleotide excision repair pathway in vivo Carcinogenesis, June 1, 2004; 25(6): 1045 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Kuang, P. E. Jackson, J.-B. Wang, P.-X. Lu, A. Munoz, G.-S. Qian, T. W. Kensler, and J. D. Groopman Specific mutations of hepatitis B virus in plasma predict liver cancer development PNAS, March 9, 2004; 101(10): 3575 - 3580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S A Khan, P L Carmichael, S D Taylor-Robinson, N Habib, and H C Thomas DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma Gut, April 1, 2003; 52(4): 586 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Kuhn and M. A. Ghannoum Indoor Mold, Toxigenic Fungi, and Stachybotrys chartarum: Infectious Disease Perspective Clin. Microbiol. Rev., January 1, 2003; 16(1): 144 - 172. [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]
|
|
|
|
|
|
W. Hu, Z. Feng, J. Eveleigh, G. Iyer, J. Pan, S. Amin, F.-L. Chung, and M.-s. Tang The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma Carcinogenesis, November 1, 2002; 23(11): 1781 - 1789. [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]
|
|