Determination of the L-ascorbic acid requirements in Wistar osteogenic disorder Shionogi rats for prolonged...

Wistar Shionogi rats of the (od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid (L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals (n = 2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 +/- 1.38 microM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 +/- 3 microM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 +/- 1.25 microM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.