Skip to main content
NCBI home page
Gut logoLink to Gut
. 1996 Mar;38(3):410–413. doi: 10.1136/gut.38.3.410

Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects.

J Meenan 1, E O'Hallinan 1, S Lynch 1, A Molloy 1, J McPartlan 1, J Scott 1, D G Weir 1
PMCID: PMC1383071  PMID: 8675095

Abstract

Localised folate deficiency has been implicated in colonic carcinogenesis and supplementation has been proposed for certain populations at risk. However, identifying those groups that may benefit is difficult as the relation between blood folate and gut epithelial cell values is unknown. The aim of this study was to define this relation. Epithelial cells mean (SEM) (sigmoid: 5.35 (0.56) x 10(6) cells, caecum: 6.6 (0.71) x 10(6) cells, duodenum: 4.0 (0.62) x 10(6) cells) were isolated from four endoscopic mucosal biopsy specimens (n = 25) by incubation with dithiothreitol (three hours) and EDTA (one hour). Lamina propria contamination was < 1%, with < 6% intraepithelial lymphocytes. Folate assay of isolates showed sigmoid colon folate content to be 20.1 (1.8) pg/micrograms DNA (10.2-46.6). In the same subject, caecal folate concentrations were lower (p < 0.01, n = 11) than sigmoid values, whereas duodenal isolates mirrored those of the sigmoid (19.4 (2.9) v 20.5 (3.2), n = 5). Sigmoid folate values were consistent over one to three weeks (n = 3). In a single case with blood folate deficiency, colonic values were normal. Serum folate and red cell folate correlated poorly with sigmoid epithelial cell folate content (r = 0.41, p = 0.063 and r = 0.17, p > 0.05 respectively). This study reports a modified ion-chelation isolation method for colonic biopsy specimens that yields large numbers of viable epithelial cells. Cell folate values remain constant with time though vary with intestinal region. The inability of serum or red cell folate values to predict those of the sigmoid epithelium suggests that they cannot identify those patients that might benefit from folate supplements.

Full text

PDF
410

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Butterworth C. E., Jr, Hatch K. D., Macaluso M., Cole P., Sauberlich H. E., Soong S. J., Borst M., Baker V. V. Folate deficiency and cervical dysplasia. JAMA. 1992 Jan 22;267(4):528–533. [PubMed] [Google Scholar]
  2. Clifford A. J., Heid M. K., Müller H. G., Bills N. D. Tissue distribution and prediction of total body folate of rats. J Nutr. 1990 Dec;120(12):1633–1639. doi: 10.1093/jn/120.12.1633. [DOI] [PubMed] [Google Scholar]
  3. Finkelstein J. D., Martin J. J., Harris B. J. Methionine metabolism in mammals. The methionine-sparing effect of cystine. J Biol Chem. 1988 Aug 25;263(24):11750–11754. [PubMed] [Google Scholar]
  4. Freudenheim J. L., Graham S., Marshall J. R., Haughey B. P., Cholewinski S., Wilkinson G. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol. 1991 Jun;20(2):368–374. doi: 10.1093/ije/20.2.368. [DOI] [PubMed] [Google Scholar]
  5. Gibson P. R., van de Pol E., Maxwell L. E., Gabriel A., Doe W. F. Isolation of colonic crypts that maintain structural and metabolic viability in vitro. Gastroenterology. 1989 Feb;96(2 Pt 1):283–291. doi: 10.1016/0016-5085(89)91549-7. [DOI] [PubMed] [Google Scholar]
  6. Kamei T., Kohno T., Ohwada H., Takeuchi Y., Hayashi Y., Fukuma S. Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium. Cancer. 1993 Apr 15;71(8):2477–2483. doi: 10.1002/1097-0142(19930415)71:8<2477::aid-cncr2820710809>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  7. Lashner B. A., Heidenreich P. A., Su G. L., Kane S. V., Hanauer S. B. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. Gastroenterology. 1989 Aug;97(2):255–259. doi: 10.1016/0016-5085(89)90058-9. [DOI] [PubMed] [Google Scholar]
  8. Lee S. K., Singh J., Taylor R. B. Subclasses of T cells with different sensitivities to cytotoxic antibody in the presence of anesthetics. Eur J Immunol. 1975 Apr;5(4):259–262. doi: 10.1002/eji.1830050408. [DOI] [PubMed] [Google Scholar]
  9. Madrigal L., Lynch S., Feighery C., Weir D., Kelleher D., O'Farrelly C. Flow cytometric analysis of surface major histocompatibility complex class II expression on human epithelial cells prepared from small intestinal biopsies. J Immunol Methods. 1993 Feb 3;158(2):207–214. doi: 10.1016/0022-1759(93)90216-t. [DOI] [PubMed] [Google Scholar]
  10. Matthews J. H., Shiels S., Wickramasinghe S. N. The effects of folate deficiency on thymidylate synthetase activity, deoxyuridine suppression, cell size and doubling time in a cultured human myeloid cell line. Eur J Haematol. 1990 Jul;45(1):43–47. doi: 10.1111/j.1600-0609.1990.tb00413.x. [DOI] [PubMed] [Google Scholar]
  11. O'Broin S., Kelleher B. Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol. 1992 Apr;45(4):344–347. doi: 10.1136/jcp.45.4.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pegg A. E. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J. 1986 Mar 1;234(2):249–262. doi: 10.1042/bj2340249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Piyathilake C. J., Hine R. J., Dasanayake A. P., Richards E. W., Freeberg L. E., Vaughn W. H., Krumdieck C. L. Effect of smoking on folate levels in buccal mucosal cells. Int J Cancer. 1992 Oct 21;52(4):566–569. doi: 10.1002/ijc.2910520412. [DOI] [PubMed] [Google Scholar]
  14. Potischman N. Nutritional epidemiology of cervical neoplasia. J Nutr. 1993 Feb;123(2 Suppl):424–429. doi: 10.1093/jn/123.suppl_2.424. [DOI] [PubMed] [Google Scholar]
  15. Rong N., Selhub J., Goldin B. R., Rosenberg I. H. Bacterially synthesized folate in rat large intestine is incorporated into host tissue folyl polyglutamates. J Nutr. 1991 Dec;121(12):1955–1959. doi: 10.1093/jn/121.12.1955. [DOI] [PubMed] [Google Scholar]
  16. Rozen P. An evaluation of rectal epithelial proliferation measurement as biomarker of risk for colorectal neoplasia and response in intervention studies. Eur J Cancer Prev. 1992 Apr;1(3):215–224. doi: 10.1097/00008469-199204000-00002. [DOI] [PubMed] [Google Scholar]
  17. Steinberg S. E. Mechanisms of folate homeostasis. Am J Physiol. 1984 Apr;246(4 Pt 1):G319–G324. doi: 10.1152/ajpgi.1984.246.4.G319. [DOI] [PubMed] [Google Scholar]
  18. Varela-Moreiras G., Selhub J. Long-term folate deficiency alters folate content and distribution differentially in rat tissues. J Nutr. 1992 Apr;122(4):986–991. doi: 10.1093/jn/122.4.986. [DOI] [PubMed] [Google Scholar]
  19. Zimmerman J. Folic acid transport in organ-cultured mucosa of human intestine. Evidence for distinct carriers. Gastroenterology. 1990 Oct;99(4):964–972. doi: 10.1016/0016-5085(90)90614-7. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES