Studies on adenovirus type 9-induced mammary fibroadenomas in rats and their malignant transformation

Abstract

After inoculating newborn W/Fu rats with adenovirus type 9, 27 of 27 females developed mammary fibroadenomas with a latency period of 14-25 weeks. No tumors were observed after inoculation with adenovirus type 5 or in males with the type 9 inoculation. After persistence of the tumors for 3-14 months, malignant transformation of the stroma resulted in different types of sarcoma in three rats: fibrosarcoma, round-cell liposarcoma, osteosarcoma and malignant mesenchymoma. In another animal the stroma of a fibroadenoma was highly cellular, suggesting a transition into fibrosarcoma. Malignant transformation of the epithelial component was not observed. Tumor cells contained adenovirus type 9-specific T-antigen, and rats with transplanted tumors were immunized to T-antigen. Mammary fibroadenomas without signs of malignant transformation developed in eight of nine female rats inoculated with adenovirus type 9 at an adult age. Neonatal thymectomy and total body x-irradiation neither significantly shortened the induction time of adenovirus 9-induced fibroadenomas nor increased the frequency of malignant transformation in females. One lipoma and one highly differentiated liposarcoma, however, appeared in two male rats. The results provide an example of the progression of a virus-induced benign tumor into a malignant neoplasm.