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

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Abstract
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 to 5–10 × 105 cells/cm, 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 × 106 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 14C-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, 3H-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.