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 (KiMSV). 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 x 10(4) to 5-10 x 10(5) cells/cm2, population doubling time during exponential growth decreased from 36-40 to 16h, acid production increased and the growth rate became independent of a reduction in serum concentration from 10% to 1%. Inoculation of 2 x 10(6) of these transformed cells into immuno-depressed 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-prognenolone showed that the transformed cells were capable of 20alpha reduction and delta5,3beta 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 K-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 K-MSV to include a secretory epithelium of mesodermal origin.
D000302:Adrenal Cortex / Q000166:cytology* / Q000473:pathology / Q000637:transplantation; D000311:Adrenal Glands / Q000166:cytology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017988:Gammaretrovirus / Q000276:immunology; D007165:Immunosuppression Therapy; D009368:Neoplasm Transplantation; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D009053:Sarcoma Viruses, Murine / Q000276:immunology; D012513:Sarcoma, Experimental / Q000209:etiology / Q000473:pathology; D014184:Transplantation, Homologous
D011374:Progesterone; D011284:Pregnenolone; D003345:Corticosterone