Transcriptional template activity of covalently modified DNA.
The transcriptional template activity of covalent modified DNA is compared. 8-Methoxypsoralen (MOP), 3,4'dimethyl-8-methoxypsoralen (DMMOP) and benzopsoralen (BP) forming with DNA covalent complexes upon UV irradiation and exhibiting preference to pyrimidines, mostly thymines, differ in their cross-linking potency. MOP and DMMOP form both monoadducts and diadducts while no cross-links are formed by BP. Nitracrine (NC) forms covalent complexes with DNA upon reductive activation with dithiothreitol exhibiting a preference to purines and low cross-linking potency. Semilogarithmic plots of the relative template activity against the number of the drugs molecules covalently bound per 10(3) DNA nucleotides fit to regression lines corresponding to one-hit inactivation characteristics. The number of drug molecules decreasing RNA synthesis to 37% differ from 0.25 to 1.26 depending on the template used and the base preference but no dependence on the cross-linking potency was found.
Tolwińska-Stańczyk
Z
Z
Department of General Chemistry, Medical University of Lódź, Poland.
Wilmańska
D
D
Studzian
K
K
Gniazdowski
M
M
D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011564:Furocoumarins / Q000494:pharmacology; D007700:Kinetics; D008730:Methoxsalen / Q000031:analogs & derivatives / Q000494:pharmacology; D009564:Nitracrine / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013698:Templates, Genetic; D014158:Transcription, Genetic
C090414:4-hydroxymethyl-4',5'-benzopsoralen; D011564:Furocoumarins; D011838:Radiation-Sensitizing Agents; D009564:Nitracrine; C067111:3,4'-dimethyl-8-methoxypsoralen; D004247:DNA; D008730:Methoxsalen