Expression of phenotypic traits following modulation of colchicine resistance in J774.2 cells

Development of resistance to colchicine in the mouse macrophage‐like cell line J774.2 coincides with the expression of a variety of phenotypic traits. A cloned subline (J7/CLC‐20), maintained in 20 μM colchicine, exhibits reduced steady‐state association with drug, increased presence of a 140,000–145,000 dalton (140–145 kD) phosphoglycoprotein associated with the plasma membrane, double minute chromosomes and cross‐resistance to other drugs. While similar phenotypic traits are observed in J774.2 cells resistant to taxol and vinblastine, differences in the electrophoretic mobilities of the resistance‐specific glycoproteins in each of the three sublines suggest that multi‐drug resistant sublines exhibit specificity for individual drugs. In an attempt to elucidate the relationships between the phenotypic traits associated with colchicine resistance, the degree of colchicine resistance in J7/CLC‐20 cells was modulated and the levels of expression of the phenotypic traits were quantitated. In the absence of colchicine in the growth medium, J7/CLC‐20 cells reverted to drug sensitivity within 35 days. A decrease in the level of resistance coincided with coordinate changes in both the quantity of the resistance‐specific glycoprotein and the average number of double minute chromosomes. We propose that the emergence and disappearance of the resistance‐specific glycoprotein and double minute chromosomes may be closely linked. However, J7/CLC‐20 cells which had regained their drug sensitivity after growth in drug‐free medium maintained a reduced level of steady‐state drug association. The persistence of reduced drug association in cells that have reverted to a drug‐sensitive state suggests that this phenomenon, although related to colchicine resistance, need not be the primary or only mechanism of drug resistance.