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. 1993 Feb;34(2):177–180. doi: 10.1136/gut.34.2.177

Conjugation of 1-naphthol in human gastric epithelial cells.

P Déchelotte 1, M Varrentrapp 1, H J Meyer 1, M Schwenk 1
PMCID: PMC1373965  PMID: 8432468

Abstract

The biotransformation of xenobiotics is essential to the maintenance of the body's integrity. Mucosal biotransformation has been well documented in the small and large intestine of animals and humans but whether the gastric mucosa plays a role in detoxifying ingested compounds remains largely unknown. The conjugation of the model phenolic compounds, 1-naphthol, by human gastric epithelial cells was assessed in vitro. Freshly isolated and cultured epithelial cells were prepared from surgical specimens obtained from patients undergoing total gastrectomy for cancer. Cell preparations were incubated with 1- 14C-naphthol over 1 hour and the glucuronide and sulphate conjugates formed were separated by thin-layer chromatography. Conjugation of 1-naphthol was observed with both freshly isolated and cultured cells. In freshly isolated cells, the 1 hour turnover of 1 microM 1-naphthol to its glucuronide and sulphate conjugates averaged 19% and 10% respectively. At higher 1-naphthol concentrations, both types of conjugate were formed at about the same rate, up to saturation (apparent Vmax = 0.07 nmol/mg protein/minute, and apparent Km = 40 microM). In cultured cells, the 1 hour turnover of 1 microM 1-naphthol to its glucuronide and sulphate conjugates averaged 35% and 8% respectively. These results suggest that the human gastric mucosa is a detoxifying organ, and that its role with regard to chemical carcinogenesis and drug first pass metabolism deserves further assessment.

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Selected References

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  1. Davis S. S., Hardy J. G., Fara J. W. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986 Aug;27(8):886–892. doi: 10.1136/gut.27.8.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dechelotte P., Schwenk M. Conjugation of phenols in human colonocytes. Gut. 1991 Aug;32(8):963–963. doi: 10.1136/gut.32.8.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Forster U., Luippold G., Schwarz L. R. Induction of monooxygenase and UDP-glucuronosyltransferase activities in primary cultures of rat hepatocytes. Drug Metab Dispos. 1986 May-Jun;14(3):353–360. [PubMed] [Google Scholar]
  4. Gibby E. M., Cohen G. M. Conjugation of 1-naphthol by human colon and tumour tissue using different experimental systems. Br J Cancer. 1984 May;49(5):645–651. doi: 10.1038/bjc.1984.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grant M. H., Burke M. D., Hawksworth G. M., Duthie S. J., Engeset J., Petrie J. C. Human adult hepatocytes in primary monolayer culture. Maintenance of mixed function oxidase and conjugation pathways of drug metabolism. Biochem Pharmacol. 1987 Jul 15;36(14):2311–2316. doi: 10.1016/0006-2952(87)90596-x. [DOI] [PubMed] [Google Scholar]
  6. Hartiala K. Metabolism of hormones, drugs and other substances by the gut. Physiol Rev. 1973 Apr;53(2):496–534. doi: 10.1152/physrev.1973.53.2.496. [DOI] [PubMed] [Google Scholar]
  7. Hänninen O., Aitio A., Hartiala K. Gastrointestinal distribution of glucuronide synthesis and the relevant enzymes in the rat. Scand J Gastroenterol. 1968;3(5):461–464. doi: 10.3109/00365526809179903. [DOI] [PubMed] [Google Scholar]
  8. Koster A. S., Frankhuijzen-Sierevogel A. C., Noordhoek J. Distribution of glucuronidation capacity (1-naphthol and morphine) along the rat intestine. Biochem Pharmacol. 1985 Oct 1;34(19):3527–3532. doi: 10.1016/0006-2952(85)90728-2. [DOI] [PubMed] [Google Scholar]
  9. Pacifici G. M., Giuliani L., Calcaprina R. Glucuronidation of 1-naphthol in nuclear and microsomal fractions of the human intestine. Pharmacology. 1986;33(2):103–109. doi: 10.1159/000138207. [DOI] [PubMed] [Google Scholar]
  10. Peters W. H., Kock L., Nagengast F. M., Kremers P. G. Biotransformation enzymes in human intestine: critical low levels in the colon? Gut. 1991 Apr;32(4):408–412. doi: 10.1136/gut.32.4.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Powell G. M., Miller J. J., Olavesen A. H., Curtis C. G. Liver as major organ of phenol detoxication? Nature. 1974 Nov 15;252(5480):234–235. doi: 10.1038/252234a0. [DOI] [PubMed] [Google Scholar]
  12. Ramakrishna B. S., Roberts-Thomson I. C., Pannall P. R., Roediger W. E. Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis. Gut. 1991 Jan;32(1):46–49. doi: 10.1136/gut.32.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schepp W., Miederer S. E., Ruoff H. J., Wulfhekel U. Isolierte menschliche Magenschleimhautzellen--Untersuchungen physiologischer und pharmakologischer Regulationsmechanismen. Klin Wochenschr. 1986 Jan 2;64(1):15–22. doi: 10.1007/BF01721576. [DOI] [PubMed] [Google Scholar]
  14. Schwenk M., Linz C., Kobusch A. B. Conjugation of 1-naphthol in the gastric mucosa of guinea pigs. Biochem Pharmacol. 1991 Jul 15;42(3):469–473. doi: 10.1016/0006-2952(91)90307-q. [DOI] [PubMed] [Google Scholar]
  15. Schwenk M., Locher M. 1-Naphthol conjugation in isolated cells from liver, jejunum, ileum, colon and kidney of the guinea pig. Biochem Pharmacol. 1985 Mar 1;34(5):697–701. doi: 10.1016/0006-2952(85)90266-7. [DOI] [PubMed] [Google Scholar]
  16. Sewing K. F., Harms P., Schulz G., Hannemann H. Effect of substituted benzimidazoles on acid secretion in isolated and enriched guinea pig parietal cells. Gut. 1983 Jun;24(6):557–560. doi: 10.1136/gut.24.6.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Soll A. H. The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells. J Clin Invest. 1978 Feb;61(2):370–380. doi: 10.1172/JCI108947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Triolo A. J., Aponte G. E., Herr D. L. Induction of aryl hydrocarbon hydroxylase and forestomach tumors ben benzo(a)pyrene. Cancer Res. 1977 Sep;37(9):3018–3021. [PubMed] [Google Scholar]
  19. WATTENBERG L. W., LEONG J. L., STRAND P. J. Benzpyrene hydroxylase activity in the gastrointestinal tract. Cancer Res. 1962 Oct;22:1120–1125. [PubMed] [Google Scholar]

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