Delayed tumor onset in transgenic mice fed a low-folate diet.
BACKGROUND
Transgenic mice carrying the human T-lymphotropic virus type 1 tax1 (transactivator) gene develop peripheral nerve sheath tumors with well-characterized times of onset and tissue involvement.


OBJECTIVE
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 tax1 gene (presence or absence), 2) gender (male or female), and 3) dietary level of folic acid (0.11 or 11.34 mumol 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 nontransgenic littermates, matched whenever possible for gender and diet.


RESULTS
Transgenic mice fed a diet containing 0.11 mumol of folic acid per kilogram developed tumors significantly later (92.8 +/- 6.4 days) than did those fed a diet containing 11.34 mumol of folic acid per kilogram (71.9 +/- 3.9 days). Folate 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.


CONCLUSIONS
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.


CONCLUSIONS
Transgenic animal models of human disease offer great potential for evaluating the role of micronutrients in human carcinogenesis.
Bills
N D
ND
Department of Nutrition, University of California, Davis.
Hinrichs
S H
SH
Morgan
R
R
Clifford
A J
AJ
D000704:Analysis of Variance; D000818:Animals; D004909:Erythrocyte Indices; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005814:Genes, Viral; D015490:HTLV-I Infections / Q000150:complications; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D016019:Survival Analysis; D013997:Time Factors
D005492:Folic Acid