Characterization of reversible, physical binding of benzo[a]pyrene derivatives to DNA.
The carcinogen, 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, and a number of its noncarcinogenic derivatives form a reversible physical complex with DNA in vitro. The absorbance spectrum of the hydrocarbon in the complex shifts approximately 10 nm to the red. Fluorescence from the physically bound hydrocarbon is significantly quenched, and binding levels are decreased by the addition of 1) spermine, 2) MgCl2, and 3) NaCl, with their relative effectiveness in reducing complex formation following the same order. Equilibrium data and the change in superhelicity of simian virus 40 DNA as a result of physical binding were used to calculate an unwinding angle for each of the benzo[a]pyrene derivatives of 13 degrees, while under the same conditions ethidium bromide unwound the duplex approximately 30 degrees. The weight of this evidence indicates that the carcinogen and its noncarcinogenic derivatives reversibly bind to DNA by intercalation of their planar aromatic system into the stacked base pairs of the duplex. The results of this and previous studies suggest that covalent binding of the carcinogenic derivative of benzo[a]pyrene to DNA is preceded by a physical intercalation step.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes; D002273:Carcinogens; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D004279:DNA, Viral; D013539:Simian virus 40; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013950:Thymus Gland
D001580:Benzopyrenes; D002273:Carcinogens; D004279:DNA, Viral; D001564:Benzo(a)pyrene; D004247:DNA