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Selection and characterization of a variant of murine L5178Y lymphoma resistant to local anesthetics
Author(s) -
Yau Tom M.,
Kim S. C.,
Crissman H. A.
Publication year - 1979
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040990211
Subject(s) - dibucaine , procaine , tetracaine , mitosis , membrane , chemistry , lidocaine hydrochloride , cell , antipain , biophysics , biology , microbiology and biotechnology , biochemistry , enzyme , lidocaine , pharmacology , protease , leupeptin , neuroscience
A variant of murine L5178Y lymphoma resistant to procaine hydrochloride (PH) was selected by exposing the cells to gradual increments of PH in the growth medium until the cell grew exponentially in the presence of 1.5 mM PH. Using cinephotomicrography, it was observed that the majority of cells that initially succumbed to PH failed to undergo successful mitosis. With respect to chromosomal, cell size distribution and flow microfluorometric analyses, the PH‐resistant cells are very similar to a spontaneous tetraploid cell line (R 1 T) previously cloned. The isolated cells, designated R 1 /P, were also found to be cross‐resistant to analogues of PH, namely, lidocaine, tetracaine and dibucaine. The naturally‐occurring tetraploid cell line (R 1 T) was also found to be more resistant to local anesthetics, although not to the same extent as R 1 /P cells. Since the enzyme that hydrolyzes procaine appears to be absent in all these lymphoid cell lines, the difference in resistance does not appear to depend on differences in the ability of these cells to remove the agent. It is suggested that an alteration in the structure and/or function of the plasma membrane in R 1 /P cells have rendered them either less sensitive to the membrane‐perturbing effects of the local anesthetics or less permeable to local anesthetics molecules. The ability of local anesthetics to affect membranes and cytoskeleton structures may play a role in the genesis and/or selection of these cell variants.