INVITRO RADIATION AND CHEMOTHERAPY SENSITIVITY OF ESTABLISHED CELL-LINES OF HUMAN SMALL CELL LUNG-CANCER AND ITS LARGE CELL MORPHOLOGICAL VARIANTS

Abstract

The in vitro response to radiation and chemotherapeutic drugs (doxorubicin, vincristine, methotrexate, 1,3-bis(2-chloroethyl)-1-nitrosourea) of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines, (NCI H187, NCI H209, NCI H249, NCI H69, NCI H146) retained the typical morphological and biochemical amine precursor uptake and decarboxylation (APUD) characteristics of SC, while 2 cell lines [NCI N417, NCI H82) had undergone transformation to large cell (LC) morphological variants with loss of cell characteristics of SC. The radiation survival curves for the SC lines were characterized by Do values ranging from 51-140 rads and extrapolation values (.hivin.n) ranging from 1.0-3.3. While the Do values of the radiation survival curves of the LC variants were similar (91 and 80 rads), the extrapolation values were 5.6 and 11.1 in vitro chemosensitivity testing of the cell lines revealed an excellent correlation between prior treatment status of the patient and in vitro sensitivity or resistance. No correlation was observed between in vitro chemosensitivity and radiation response. Transformation of SC to LC with loss of APUD characteristics is associated with a marked increase in radiation resistance (.hivin.n) in vitro. The observation of a 2- to 5-fold increase in survival of the LC compared to the SC lines following 200 rads suggests that the use of larger daily radiation fractions and/or radiation-sensitizing drugs might lead to a significantly greater clinical response in patients with LC morphology. This clinical approach may have a major impact on patient response and survival.