PHENOTYPICALLY VARIANT ADRENAL TUMOR CELL CULTURES WITH BIOCHEMICAL LESIONS IN ACTH-STIMULATED STEROIDOGENIC PATHWAY

Four clonal adrenal tumor cell lines which exhibit biochemical lesions in the ACTH‐stimulated steroidogenic pathway have been isolated. Two of these cell lines, designated Y‐6 and OS3, appear to contain their lesions at points proximal to cyclic AMP formation in the ACTH‐stimulated steroidogenic pathway. Growth of Y‐6 and OS3 as tumors in isogenic mice results in a restoration of ACTH sensitivity in both cell lines by mechanisms which do not appear to involve selection or fulfillment of specific nutritional requirements. Growth of Y‐6 and OS3 as tumors in heterogenic mice results in restoration of ACTH sensitivity in Y‐6 but not in OS3, suggesting that the biochemical lesions in these cell lines are at different loci. Two other cell lines, designated OS1 and OS4, possess biochemical lesions in the steroidogenic pathway beyond the formation of cyclic AMP and before the formation of pregnenolone. Growth of OS1 and OS4 as tumors in isogenic mice results in the repair of the biochemical lesions in these cells distal to cyclic AMP formation in the ACTH‐stimulated steroidogenic pathway. The four cell lines described are potentially useful in elucidating the mechanism of action of ACTH in adrenal cells as well as in determining the factors required for maintaining differentiated function in cultured cells. Copyright © 1969 Wiley‐Liss, Inc.