Transformation of cultured rat adrenocortical cells by kirsten murine sarcoma virus (ki‐msv)

Two‐week‐old primary cultures of normal adult rat adrenal cortex were exposed to Kirsten murine sarcoma virus (Ki‐MSV). Within a week, the adrenal cells, which are normally fusiform and aligned in parallel, became pleomorphic and piled up extensively. Saturation density increased from 5–10 × 10<4> to 5–10 × 10 5 cells/cm<2>, population doubling time during exponential growth decreased from 36–40 to 16 h, acid production increased and the growth rate became independent of a reduction in serum concentration from 10% to 1%. Inoculation of 2 × 10 6 of these transformed cells into immunodepressed rats produced rapidly growing tumors within 1 week. Histologically, the tumors were pleomorphic carcinomas with areas ranging from anaplasia to near‐normal, highly differentiated adrenocortical tissue. In addition to histologic evidence of differentiation, metabolic studies using 14 C‐pregnenolone showed that the transformed cells were capable of 20α reduction and Δ5,3β dehydrogenation, both characteristic of normal steroid‐secreting tissues. The transformed adrenocortical cells produced infectious C‐type virus as indicated by electron microscopy, 3 H‐uridine incorporation, and focus formation in NRK (normal rat kidney) cultures. The neutralization pattern of this virus resembled that of authentic Ki‐MSV. The transformation of adrenocortical cells by Ki‐MSV demonstrates the capacity of this agent to induce carcinomas in differentiated cells after short‐term culture, and widens the range of tissues known to be susceptible to Ki‐MSV to include a secretory epithelium of mesodermal origin.