DETERMINATION OF THE L-ASCORBIC-ACID REQUIREMENTS IN WISTER OSTEOGENIC DISORDER SHIONOGI RATS FOR PROLONGED CARCINOGENESIS EXPERIMENTS

Wistar Shionogi rats of the (od/od) substrain with the osteogenic diso rder 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 carcino genesis. To determine the minimal L-AA requirements of these animals f or prolonged survival in a satisfactory physical condition during expe rimentation, 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 we ekly 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 simula te the procedures to be undertaken in oral mucosal carcinogenesis expe riments, 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 mu M, approxima tely one-eighth that of the normal level (mean plasma L-AA level in ou tbred Wistar rats was found to be 58 +/- 3 mu M) whilst those in the h igher supplement group (3.33 g/l L-AA) achieved a mean of 18 +/- 1.25 mu M. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA. deficiency during this pe riod.