A comparison of the relative activities of 8 radiosensitizers in the SOS chromotest.
Misonidazole, and RSU 1069 and 6 of its analogues are all reported to show increased cytotoxicity towards hypoxic cells compared to oxic cells. DNA is considered to be the target through which these drugs exert their cytotoxic activity. Therefore we monitored induction of the SOS response in uvrABC excinuclease proficient and deficient strains of E. coli, under oxic and hypoxic conditions, as an indirect method of assessing the activity of these drugs towards DNA in a biological system. This was done using the SOS chromotest which utilizes E. coli strains which possess a sfiA::lacZ fusion allowing induction of the SOS response to be monitored by assaying beta-galactosidase activity. All of the drugs tested here show some induction of the SOS response in both uvrABC excinuclease proficient and deficient strains. Data shown here suggests that the uvrABC excinuclease is important in the production of a SOS induction signal from RSU 1069-induced DNA lesions and that RSU 1069 may act as a crosslinking agent. The data also shows that SOS induction activity and toxicity do not necessarily correlate and that production of a SOS induction signal may occur via a different pathway for RSU 1069 than for its analogues.
Widdick
D A
DA
Chemotherapy Research Unit, Polytechnic of East London, Great Britain.
Edwards
D I
DI
D015687:Cell Hypoxia; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D013014:SOS Response, Genetics
D011838:Radiation-Sensitizing Agents; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole