Carcinogenesis Advance Access published online on September 11, 2003
Carcinogenesis, doi:10.1093/carcin/bgg150
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St. Boston MA, 02111
* Corresponding author. E-mail: jimmy.crott{at}tufts.edu.
Received 10 June 2003
; revised 1 August 2003
; accepted 11 August 2003
Folate depletion and aging are risk factors for colorectal cancer. We investigated the effects of folate status and aging on gene expression in the rat colon. Young (weanling) and elder (12 month) rats were fed folic acid deplete (0 mg/kg) and supplemented (8 mg/kg) diets for 20 weeks. Gene expression was measured in colonic mucosal scrapings (n = 3/group) using oligonucleotide arrays (Affymetrix U34A). Folate depletion induced the up-regulation of immune-related genes, urokinase and inducible nitric oxide synthase and the down-regulation of adhesion molecules (protocadherin-4, nidogen, integrin alpha V) and vascular endothelial growth factor in young rats. The abbreviated response to depletion in old rats (62 changes v 136 in the young) included up-regulation of caspase-2 and DCC (deleted in colon cancer). Gene expression changes due to aging were more abundant in folate deplete than supplemented rats (38 v 119 genes respectively). In folate deficient rats, aging induced the down-regulation of immune-related genes, urokinase, p53, insulin-like growth factor binding protein-3 and vav-1 oncogene. In folate supplemented rats, aging induced the down-regulation of vascular endothelial growth factor and caspase-2. Lower expression of adhesion molecules and higher expression of urokinase with folate depletion in young rats may indicate that cell detachment and migration, cancer-related processes, may be modulated by folate status. An age-related decline in p53 and IGF-BP3 expression was only observed in folate deplete animals, indicating that folate supplementation may reduce the risk for age-associated cancers by suppressing deleterious changes in the expression of certain genes.
Folate, gene expression, colon, rat, aging
Effects of dietary folate and aging on gene expression in the colonic mucosa of rats: implications for carcinogenesis
2 Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St. Boston MA, 02111
3 Department of Pathology, Tufts-New England, Medical Center, Boston MA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Marsillach, N. Ferre, J. Camps, F. Riu, A. Rull, and J. Joven Moderately High Folic Acid Supplementation Exacerbates Experimentally Induced Liver Fibrosis in Rats Experimental Biology and Medicine, January 1, 2008; 233(1): 38 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Kim and J. A. Milner Dietary Modulation of Colon Cancer Risk J. Nutr., November 1, 2007; 137(11): 2576S - 2579S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Novakovic, J. M. Stempak, K.-J. Sohn, and Y.-I. Kim Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells Carcinogenesis, May 1, 2006; 27(5): 916 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jang, J. B. Mason, and S.-W. Choi Genetic and Epigenetic Interactions between Folate and Aging in Carcinogenesis J. Nutr., December 1, 2005; 135(12): 2967S - 2971S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chanson, T. Sayd, E. Rock, C. Chambon, V. Sante-Lhoutellier, G. Potier de Courcy, and P. Brachet Proteomic Analysis Reveals Changes in the Liver Protein Pattern of Rats Exposed to Dietary Folate Deficiency J. Nutr., November 1, 2005; 135(11): 2524 - 2529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Davis and N. G. Hord Nutritional "Omics" Technologies for Elucidating the Role(s) of Bioactive Food Components in Colon Cancer Prevention J. Nutr., November 1, 2005; 135(11): 2694 - 2697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W.L. Ma, R. H. Finnell, L. A. Davidson, E. S. Callaway, O. Spiegelstein, J. A. Piedrahita, J. M. Salbaum, C. Kappen, B. R. Weeks, J. James, et al. Folate Transport Gene Inactivation in Mice Increases Sensitivity to Colon Carcinogenesis Cancer Res., February 1, 2005; 65(3): 887 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Cabelof, J. J. Raffoul, J. Nakamura, D. Kapoor, H. Abdalla, and A. R. Heydari Imbalanced Base Excision Repair in Response to Folate Deficiency Is Accelerated by Polymerase {beta} Haploinsufficiency J. Biol. Chem., August 27, 2004; 279(35): 36504 - 36513. [Abstract] [Full Text] [PDF]
|
|