Inhibitory effect of membrane-binding drugs on excision repair of DNA damage in UV-irradiated Escherichia coli.

The effects of procaine and lidocaine on DNA-repair processes were investigated in UV-irradiated cells of E. coli with different DNA-repair capacities. The cells were irradiated with various doses of UV and then incubated at 37 degrees C in M9 buffer (liquid-holding) or in EM9 medium in the presence or absence of membrane-binding drugs. The results obtained are as follows. (1) In strains H/r30 (wild-type for DNA repair) and NG30 (recA-), the increase in survival with increase in time of liquid-holding was almost completely inhibited by the addition of procaine and lidocaine. The same trends were observable under conditions of post-irradiation incubation in EM9 medium, more efficiently in recA- strain than in the wild-type strain. (2) The addition of these drugs gave an apparent enhancement of the frequency of UV-induced mutation to arginine prototrophy, corresponding to a decrease in survival. (3) There were negligible effects of the drugs on survival and mutation in the excision-repair-defective strain, Hs30 (uvrB-). (4) The removal of thymine dimers from DNA was actually reduced by the addition of procaine. From these results it is concluded that procaine and lidocaine inhibited excision-repair process in UV-irradiated E. coli cells. Procaine and lidocaine are typical local anesthetics and known to interact with cell membranes causing alterations in the structural and functional organization. Therefore, it is suggested that a disorganization of the membrane structure brought about by the drugs may result in an inhibition of excision repair of DNA damage in E. coli, assuming that at least a component of excision repair is associated with the cell membrane. Possible mechanisms involved in this process are discussed.