Relationships between neuroendocrine differentiation and sensitivity to gamma-radiation in culture line OH-1 of human small cell lung carcinoma.

After 16 months, an established line of human small cell lung cancer (OH-1) underwent a subtle morphological change which was associated with a virtually complete loss of neuroendocrine differentiation as judged by electron microscopy studies and a 12-fold loss in L-dopa decarboxylase activity. In nude (athymic) mouse heterotransplants, the histology of the early-passage cells (oat or lymphocyte-like) differed only slightly from the late-passage cells (intermediate or polygonal type); cytology studies showed no diagnostic differences between the passages. However, the early-passage endocrine-like cells showed up to 100-fold less cell survival after irradiation than the late-passage cells. Thus, subtle changes in the morphology of OH-1 cells are accompanied by a profound loss of neuroendocrine differentiation and the emergence of radiation resistance. These changes could have important parallelisms for behavior of small-cell lung carcinoma in humans. The cell culture model described may be useful in investigating the interrelationships occurring between endocrine and nonendocrine cells in the spectrum of human lung cancer. The findings emphasize that neuroendocrine-related ultrastructure and biochemistry may help define important cell populations in lung cancer with respect to therapeutic sensitivity.