Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line.

Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line.

small cell lung cancer

fetal calf serum

serum‐supplemented medium (RPMI 1640 and 10% FCS)

delipidized FCS

delipidized serum‐supplemented medium (RPMI 1640 and 10% DL‐FCS)

aromatic l‐amino acid decarboxylase, NSE, neuron‐specific enolase

creatine kinase, brain isoenzyme

dimethylsulfoxide

phosphate‐buffered saline (137 mM NaCl, 3 mM KC1 and 10mM phosphate buffer pH 7.0)

trichloroacetic acid