The in vitro interaction with DNA of several hypoxic radiosensitizers.
The five 5-nitroimidazole derivatives and the four glyoxylic compounds tested in this paper for their interaction with DNA with and without irradiation had previously been reported to act as radiosensitizers at a cellular level. Our aim was to find if the radiosensitizing activity of these products could be due to their interaction with DNA. For this purpose the formation of a complex was tested by comparing the spectrophotometrical absorbances of (DNA-product) solutions with those of DNA and of the products, at the absorption maxima of the products. None of the products formed in vitro a complex with DNA. The irradiation of product solutions with and without DNA induced a molecular degradation of the product which was linearly correlated with the radiation dose. The G values characterizing this radiodegradation showed that the presence of DNA did not modify the radiosensitivity of the products, neither in aerobic nor under hypoxic irradiation conditions. These results proved that the radiosensitizing properties of these compounds cannot be attributed to their chemical interaction with DNA.
Santos Peinado
L
L
Instituto de Química Física Rocasolano, CSIC, Madrid, Spain.
Cornago Ramirez
P
P
Lopez Zumel
C
C
D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006038:Glyoxylates / Q000494:pharmacology; D000860:Hypoxia; D009593:Nitroimidazoles / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014965:X-Rays
D006038:Glyoxylates; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D004247:DNA