Effect of dilantin in mice

Abstract

Four hundred and thirty two mice of strains C3H/f, C57Bl, and SJL/J were divided into 9 groups and fed normal mouse pellets, a liquid chocolate flavored diet (Metrecal), and the liquid diet with dipenyl hydantoin, respectively, over a period of 16 months. An additional 60 C67Bl mice were sensitized with bovine serum albumin (BSA) and complete Freund's adjuvant while on dipenyl hydantoin and studied for their humoral and cellular immune reactivity by passive hemagglutination microassays and foot-pad tests. Mice of all 3 strains showed lesions in their lymphoreticular tissues from the second month of the experiment on, varying from partial activation to atrophy. Primarily affected was the paracortical zone of lymph nodes. C3H/f and C57Bl mice developed thymic lymphosarcomas with a frequency of 3 of 24 mice each. SJL/J mice also showed similar tumors early during the experiment, i.e. 6 of 42 mice during the 4th to the 8th month. After the 8th month SJL/J mice developed up to 90% reticulum cell sarcomas type B, a lesion known to occur in these mice in a high frequency; however, its occurrence was about 2–3 months earlier than usual. Immunologic studies in dipenyl hydantoin fed mice revealed variable but not significantly decreased serum anti-BSA titers while the foot-pad tests were constantly negative for a delayed hypersensitivity reaction. It is concluded from these results that diphenyl hydantoin accelerates the spontaneous development of lymphoma in susceptible animals and may also induce such tumors at low frequencies. The mode of action probably is through interference with the normal immune response by simultaneous immunostimulation and immunosuppression.