Selection of a dexamethasone-resistant H-4-IIE-C3 rat hepatoma tissue-culture line

Summary Exposure of H-4-IIE-C3 rat hepatoma cell cultures to the synthetic glucocorticoid, dexamethasone, results in an inhibition of cellular proliferation which is not the result of steroid-induced cytolysis. A significant decrease in both the rat of DNA synthesis and DNA content precedes, a detectable effect on cell number. Continuous culture of H-4-IIE-C3 cells in medium containing 10⁻⁵ m dexamethasone results in the selection of a steroid-resistant cell population that has the growth characteristics of unselected sensitive cultures and shows normal steroid induction of tyrosine transaminase. Selection is a slow process requiring 24 to 36 months to obtain, a phenotypically stable resitant cell line, and can be subdivided into three phases—a sensitive phase, adaptation and resistance. A comparison of the karyotypes of unselected and resistant cultures shows that the selection process enriches for a dexamethasone-resistant subpopulation. This work was supported by Special Grant No. 716 from the California Division of the American Cancer Society, and a grant-in-aid from the San Diego State University Foundation.