GM food debate
1999; Elsevier BV; Volume: 354; Issue: 9191 Linguagem: Inglês
10.1016/s0140-6736(99)90199-x
ISSN1474-547X
Autores Tópico(s)Transgenic Plants and Applications
ResumoStanley Ewen and Arpad Pusztai (Oct 16, p 1353)1Ewen SWB Puszati A Effects of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine..Lancet. 1999; 354: 1353Summary Full Text Full Text PDF PubMed Scopus (316) Google Scholar raise intriguing questions about the potential of Galanthus nivalis agglutinin (GNA) to cause morphological alterations in the intestinal tract and suggest that the lectin's effects may be exacerbated in genetically modified potatoes. However, the ways in which Ewen and Pusztai assess the enteropathic properties of GNA mean that their findings must be interpreted with extreme caution. The indices of crypt length and jejunal intraepithelial lymphocyte (IEL) count have been used to study intestinal immunopathology for 20 years or more2Mowat AM Ferguson A Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine..Gastroenterology. 1982; 83: 417-423Summary Full Text PDF PubMed Scopus (88) Google Scholar, 3Ferguson A Models of immunologically-driven small intestinal damage..in: Marsh MN Immunopathology of the small intestine. Wiley, Chichester1987: 225-252Google Scholar but several aspects of Ewen and Pusztai's methodology warrant attention. First, the study relies entirely on image analysis of formalin–fixed, paraffin-embedded sections, which are notoriously subject to shrinkage, distortion, and other fixation artifacts. These problems can be partly overcome by careful choice of well-oriented villuscrypt units combined with exhaustive measurement techniques, but Ewen and Pusztai do not indicate whether they did this. Errors created by measuring crypts in different planes of section on the sample could account for the high variation reported. The fact that the crypt lengths reported (60-90 μm in the jejunum) are much smaller than those normally found in the rat4Clarke RM Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat..J Anat. 1970; 107: 519-529PubMed Google Scholar reinforces the view that the measurements may not have been accurate. More sensitive methods for processing and measuring intestinal tissues include non-formalin-based fixatives, microdissection, and direct morphometry of crypt and villus lengths.2Mowat AM Ferguson A Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine..Gastroenterology. 1982; 83: 417-423Summary Full Text PDF PubMed Scopus (88) Google Scholar, 3Ferguson A Models of immunologically-driven small intestinal damage..in: Marsh MN Immunopathology of the small intestine. Wiley, Chichester1987: 225-252Google Scholar, 4Clarke RM Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat..J Anat. 1970; 107: 519-529PubMed Google Scholar The enterocyte mitotic rate is probably the most sensitive index of intestinal pathology,2Mowat AM Ferguson A Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine..Gastroenterology. 1982; 83: 417-423Summary Full Text PDF PubMed Scopus (88) Google Scholar and this can be measured easily by metaphase arrest or incorporation of bromodeoxyuridine. Ewen and Pusztai use IEL counts to support their hypothesis that genetically modified potatoes cause jejunal lesions. They state that “IEL are known to increase when non-specific intestinal damage occurs”, but an increase in IEL count is specifically a feature of enteropathies associated with activated T lymphocytes.3Ferguson A Models of immunologically-driven small intestinal damage..in: Marsh MN Immunopathology of the small intestine. Wiley, Chichester1987: 225-252Google Scholar Thus an increased IEL count in animals receiving lectins could be compelling evidence for these materials inducing immunologically mediated damage to the gut. However, Ewen and Pusztai have not shown this conclusively. They do not seem to have counted IELs by a well-established method in which IEL are counted per 100 enterocyte nuclei or as an absolute number per length, volume or area of mucosa. That the technique they used is not ideal is underlined by the numbers of IEL they report, which are in the region of 7-11 per 48 villi. To reconcile these estimates, given that a single column of villus enterocytes in the rat jejunum contains 200-300 enterocytes and the density of IEL in the normal small intestine is 10-20 per 100 epithelial cells, is difficult. The low protein content of some of the diets, referred to by other commentators as a possible source of error,5Kuiper HA Noteborn HPJM Peijneburg AACM Adequacy of methods for testing the safety of genetically modified foods..Lancet. 1999; 354: 1354Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar could account for some deviation of IEL numbers from normal but not for such a gross change. However, it is feasible that such a diet might have made the rats more susceptible to the intestinal infections known to cause the kind of changes in IEL and crypts3Ferguson A Models of immunologically-driven small intestinal damage..in: Marsh MN Immunopathology of the small intestine. Wiley, Chichester1987: 225-252Google Scholar noted here. The speculation that the lectin caused jejunal crypt hyperplasia via a direct stimulatory effect on crypt cells cannot be substantiated by the data. Hyperplasia implies increased mitotic activity, which was not measured. Also, the time course for these changes is not described, and no parameters of villus pathology are provided. In the absence of this information, it is impossible to say whether the changes in crypt morphology are primary effects of the lectin or secondary to villus damage. Interactions between lectins, intestinal epithelial cells, and the local immune apparatus is an important and poorly understood area. Appropriate methods for studying the enteropathic effects of lectins are available and are comparatively simple and inexpensive. Application of these techniques may help elucidate the issues raised by this provocative study. GM food debateAuthors' reply Full-Text PDF
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