Localization of specific [3H]dexamethasone binding in urethan-induced mouse lung tumors

Pulmonary tumors induced in A/J mice 14 months after a single i.p. injection of urethan vary greatly in size. Since glucocorticoids may play a major role in regulating lung cell proliferation, glucocorticoid binding was examined in these tumors to determine whether tumor size was related to any specific pattern of [3H]dexamethasone [( 3H]DEX) binding. Tumor samples were incubated in vitro with 17 nM [3H]DEX for 90 min at 37 degrees, washed extensively to reduce nonspecific binding, and either fractionated by differential centrifugation to quantify nuclear and cytosolic binding or processed for autoradiography. Quantitative binding studies demonstrate a reduction in specific nuclear [3H]DEX binding and an increase in nonspecific cytosolic binding in all of the tumors examined as compared to normal adult lung. Autoradiographic studies reveal pulmonary tumors of different morphology which vary in their [3H]DEX binding characteristics. Small tumors were of two histological patterns, alveolar adenomas which are probably derived from alveolar type II cells and papillary adenomas which are probably derived from bronchiolar Clara cells. The alveolar adenomas contain little nuclear [3H]DEX binding, whereas the papillary adenomas show extensive nuclear localization of [3H]DEX. These results indicate that nuclear localization of [3H]DEX can provide a biochemical criterion for distinguishing alveolar from papillary adenomas. Most of the larger tumors were either papillary or anaplastic in morphology and localized [3H]DEX in their nuclei. This suggests that these larger and possibly more malignant tumors are derived from papillary adenomas.