The last gift.
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Biomedical subjects
Publications and source records attributed to E P Seravalli.
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Chloroprocaine, an aminoester local anesthetic commonly used for epidural block, has been found to induce interspecies somatic cell hybrids in vitro. Mixed cultures of human amniocytes and mouse hepatoma cells, deficient in hypoxanthine phosphoribosyl transferase, were exposed to 1.6, 0.8, or 0.4 X 10(-3)M chloroprocaine for 3 hr at 37 degrees C, then maintained for 3 weeks in a double-selective medium of hypoxanthine, aminopterin, and thymidine (HAT) and ouabain to eliminate the unfused parental cells. Clones of actively multiplying cells appeared in cultures exposed to 1.6 and 0.8 X 10(-3)M chloroprocaine. Chromosome analysis confirmed they were hybrids. Cultures treated with 0.8 X 10(-3)M chloroprocaine exhibited the highest frequency of cell hybridization (8.8 X 10(-5). The hybrid clones bore the morphologic characteristics of both parents although their growth pattern closely resembled the mouse parent. Procaine, sodium bisulfite (the antioxidant present in the commercial solutions of chloroprocaine), and the two chloroprocaine metabolites, chloroaminobenzoic acid and diethylaminoethanol, were nonfusogenic. The hybridogenic effect of chloroprocaine has not been previously described with other local anesthetics.
The cytotoxicity of the local anesthetics chloroprocaine, procaine, and lidocaine was studied in murine and human cells. Murine glial and hepatic cells, and human fibroblasts were individually exposed to chloroprocaine, procaine, and lidocaine in concentrations ranging from 1.6 X 10(-3) M to 0.2 X 10(-3) M. The cells of all three cell lines underwent membrane fusion after exposure to chloroprocaine as indicated by the presence of the high number of multinucleated cells in the cultures. The 0.8 X 10(-3) M concentration was the most fusogenic, and caused multinucleation in 30% of glial and hepatic cells, and in 23% of fibroblasts. Membrane fusion and multinucleation also occurred in mixed human and murine cell cultures that were exposed to 0.8 X 10(-3) M concentration of both commercial and crystalline solutions of chloroprocaine, with a portion of multinucleated cells that was 27 and 17%, respectively. Cell membrane fusion was not caused by procaine, lidocaine, sodium bisulfite (the antioxidant present in the commercial solutions of chloroprocaine), or chloro-aminobenzoic acid and diethylamino-ethanol (the two chloroprocaine metabolites). The fusogenic effect of chloroprocaine on cell membrane has not been previously described for any local anesthetic.