Osteomas in OF-1 mice: no alteration in biologic behavior during long-term treatment with cyclosporine.
During the course of a long-term oral study in OF-1 mice for the assessment of any carcinogenic potential of the immunosuppressive agent cyclosporine (CS-A), a high incidence of osteomas was found in all treatment groups as well as in controls. The incidences of osteoma-bearing mice were 20% in control male and 30% in control female mice; the respective incidences in all treated mice were 14.7% for males and 38% for females. The osteomas were found to occur in multiple sites in 70% of control males, in 73.3% of control females, and from all treated groups in 54.5% of males and 64.9% of females. The pelvis and sacrum were most frequently involved (42%), followed by the hindlimbs (32%), the skull (14.5%), the vertebral column (6.5%), the forelimbs (4%), and the sternum and ribs (1%) in control animals. The distribution of osteomas was similar in treated mice and did not differ significantly from controls. Histologic and ultrastructural analysis confirmed benign osteomas with abundant C-type viral particles. Thus a previously unobserved spontaneous high incidence of osteomas was reported in OF-1 mice. Immunosuppressive treatment with CS-A did not change the incidence or the biologic behavior of these osteomas.