Abstract
In order to elucidate the mechanism of action of new antitumor agents like bis-(haloalkyl) piperidine derivatives, sensitivity of various deoxyribonucleic acid (DNA) repair-deficient mutants of Eschericha coli B to these derivatives was examined. When bacteria were treated with 1-(β-chloroethyl)-2-chloromethylpiperidine hydrobromide (CAP-1), ultraviolet-sensitive (uvrA-) mutant and recombination-deficient (recA-) mutant were killed and DNA polymerase I-minus (pol I-) mutant was moderately killed. The killing kinetics of CAP-1 on bacteria was very similar to those of ultraviolet ray. These reapir-deficient mutants were remarkably sensitive to 1-(γ-chloropropyl)-2-chloromethyl-piperidine hydrobromide (CAP-2), and its killing kinetics was similar to those of mitomycin-C. Moreover, in the case of 2, 6-bis (iodomethyl) piperidine hydrochloride (CAP-12), pol I- mutant was very rapidly killed and recA- and uvrA- mutants were moderately killed, though the viability of wild type strain was hardly affected. These results indicate that the higher sensitivity of repair-deficient E. coli mutants to bis (haloalkyl) piperidine derivatives is mainly due to their impaired repair ability for DNA damage caused by these derivatives. Therefore, it is concluded that these derivatives act on bacterial DNA and produce DNA lesions repairable by the repair systems of the wild type strain.
