Tissue concentrations and proliferative effects of massive doses of ascorbic acid in the mouse

The effect of ascorbic acid supplementation on CF1 mice fed ascorbic acid for approximately six months at dose levels of 1%, 5%, and 10% of diet was investigated by analysis of tissue ascorbic acid concentration in the liver, kidney, stomach, small intestine, and large bowel. The effect on epithelial cell proliferation was also examined in the small and large bowel but only at the 5% level. In the control animals, ascorbic acid concentration was lowest in the liver (0.406 +/- 0.07 mg/g) and highest in the small bowel (0.754 +/- 0.16 mg/g). Dietary intake of 5% and 10% ascorbic acid significantly elevated levels in the liver (0.741 +/- 0.13; p less than 0.05), and all doses of ascorbic acid significantly raised tissue concentrations in the kidney and colon. No difference was observed in the percentage of DNA-synthesizing cells in the jejunum of controls or animals fed 5% ascorbic acid at 1 or 24 hours after 3HTdR injection. However, at 1 hour a significantly decreased level of proliferation was observed in the distal colon of ascorbic-acid-treated mice compared with controls (labeling index [L.I.] = 7.3 +/- 0.28 vs. 10.1 +/- 1.15; p less than 0.05), and an even greater suppression of DNA synthesis was achieved by 24 hours (L.I. = 11.4 +/- 1.06 vs. 18.6 +/- 1.61; p less than 0.01). None of the doses of ascorbic acid employed was toxic to the experimental mice.