© 1992 by Oxford University Press
Journal of the National Cancer Institute, Vol. 84, No. 5, 332-337,
March 4, 1992
© 1992 Oxford University Press
Delayed Tumor Onset in Transgenic Mice Fed a Low-Folate Diet
Department of Nutrition, S. H. Hinrichs, R. Morgan Department of Medical Pathology), University of California Davis.
Department of Medical Pathology, University of California Davis.
* Correspondence to: Andrew j. Clifford, Ph. d., Department of Nutrition University Of California Davis, CA 95616-8669
Background: Transgenic mice carrying the human T-lymphotropic virus type 1 tax 1(transactivator) gene develop peripheral nerve sheath tumors with well-characterized times of onset and tissue involvement. Purpose and Methods: To evaluate the effect of dietary folic acid on age at tumor onset and on the concentration of folate in tissues and tumors, we bred heterozygous transgenic mice and systematically assigned their offspring at weaning (within litters) to a 2 x 2 x 2 factorial arrangement. The three variables studied were 1) the tax, gene (presence or absence), 2) gender (male or female), and 3) dietary level of folic acid (0. 11 or 11.34 µmol folic acid per kilogram of controlled amino acid-based diet). Blood and tissues were collected from tumor-bearing transgenic mice (prior to cachexia) and from non-transgenic littermates, matched whenever possible for gender and diet. Results: Transgenic mice fed a diet containing 0. 11 µmol of folic acid per kilogram developed tumors significantly later (92. 8 ± 6. 4 days) than did those fed a diet containing 11. 34 µmol of folic acid per kilogram (71. 9 ± 3. 9 days). Fo-late concentrations in tumors of mice fed the low-folate diet were approximately one third those in tumors of mice fed the higher folate diet. Brain folate concentrations in mice fed the low-folate diet were less than one half those in mice fed the higher folate diet. Conclusion: Results show that the onset of spontaneous tumors can be delayed by feeding mice the lowest level of folate adequate to meet nutritional requirements for normal growth. Implication: Transgenic animal models of human disease offer great potential for evaluating the role of micronutrients in human carcinogenesis. [J Natl Cancer Inst 84: 332–337, 1992]
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