Bacterial DNA reactivity of the novel antitumor antibiotics PD 114,759 and PD 115,028 (veractamycins A and B).
The novel antitumor antibiotics PD 114,759 and PD 115,028 were evaluated for their ability to cause repairable DNA damage and the induction of SOS functions in bacterial systems. PD 114,759 and PD 115,028 were preferentially toxic to DNA repair-defective Escherichia coli WP100 uvrA recA in comparison to wild-type E. coli WP2 at concentrations of 10 approximately 30 micrograms/ml in agar diffusion assays. Both compounds were inducers of cell filamentation and prophage lambda (two E. coli SOS functions) at concentrations of 0.1 approximately 1 microgram/ml. In addition, the ability of PD 114,759 and PD 115,028 to retain their filamentation-inducing effects under both aerobic conditions and anaerobic conditions suggests that a bioreductive, rather than an oxygen-requiring, mechanism is involved in the DNA-reactive effects of these agents.
Mamber
S W
SW
Okasinski
W G
WG
Pinter
C D
CD
Tunac
J B
JB
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001688:Biological Products; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D001688:Biological Products; D004269:DNA, Bacterial; C044530:veractamycin A; C044531:veractamycin B