Inhibition of growth of Shope rabbit papilloma by hypervitaminosis A.

entiation of epithelial cells. Deficiency of vitamin A causes squamous metaplasia of columnar epithelium (11, 13). Excess vitamin A causes conversion of some nor mally keratinizing epithelia to a columnar, secretory type (1, 9). In addition, vitamin A has been shown to influ ence the morphology of myxoviruses (4). In view of these effects, it was of interest to determine whether high doses of vitamin A would influence the development of the Shope rabbit papifioma, a virus-induced, epithelial neo plasm. per week to 28 young adult New Zealand white rabbits of both sexes and to 6 wild rabbits from Kansas. Control solutions were administered to corresponding numbers of New Zealand and wild rabbits. Observations of the fol lowing were made on the New Zealand rabbits : (a) the time to macroscopic appearance of papifiomas (incubation period); (b) the height of the fleshy portions of the papil lomas (conalsting principally of viable, nonkeratinized epithelium with a small amount of vascularized connective tissue stroma) ; and (c) the presence or absence of perma nent papilloma regression. Observations of the effect of vitamin A on virus titer were made on the wild rabbits. The dosage of vitamin A used was high enough to cause toxicity, as indicated by substantial weight loss and mor tality. The vitamin-treated rabbits lost an average of 27 % of their initial weight in an average interval of 48 days, compared to a 1 % weight gain for the control rab bits during the same period. The mortality was 55 % for the vitamin-treated rabbits, with death occuring 7†" 96 days following start of treatment, compared with a 13 % mortality for the control rabbits. Treatment schedules were as follows: Group 1.†" Two New Zealand rabbits, initially 2.0 and 2.7 kg each, received vitamin A palinitate (Aquasol A),2 250,000 IU per injection, starting 15 and 23 days after virus inoculation, for 26 and 22 days respectively. Group 11.†" Five New Zealand rabbits, initially 2.0 to 2.7 kg each, received, starting 26 days after virus inocula tion, vitamin A palmitate (Aquasol A), 250,000 IU per injection for 27 days, followed by 150,000 lU/kg/injection for 16 days, followed by vitamin A alcohol,3 144,000 IU/ kg/injection for 27 days. (Total treatment duration was 39†" 70days, depending on survival.) Group 111.†" Five New Zealand rabbits, initially 3.1 to 3.6 kg each, received, starting 63†" 71 days after …