[In vitro inhibition of DNA replication by local anesthetics. Effects on human MCF7 neoplastic cells]

The action of two local anesthetics (Lidocaine and Bupivacaine) on cells of mammary carcinoma MCF7 was investigated. 3H-TdR incorporation decreases in relation to the dose, and viability by Trypan blue does not significantly change but at high doses of anesthetic. Intercell adhesion decreases only at high concentration. When Lidocaine is removed after the fourth hour and Bupivacaine after the second hour the antimitotic action is irreversible. The inhibiting action of drugs is related to the cell number and unrelated to the time of adding the drug. There was no change of Lidocaine and Bupivacaine action on neoplastic cells at different concentration of Na+, K+ and Ca++ in the medium. Neoplastic cells are partially independent from Ca++ and we think the antimitotic effect of local anesthetics we observed can be due to: antagonist action to calmodulin; inhibition of aminoacylation of tRNA; inhibition of cholesterol synthesis; modification of membrane permeability which is however significant only for high concentration of the drug.