Binding of benzo(a)pyrene metabolite(s) to main and satellite calf thymus DNA's in vitro

It has been proved that carcinogens bind to macromolecules of the target tissues [ 1,2] and that a positive correlation exists between the extent of binding of hydrocarbons to DNA and their carcinogenic properties [3] . The binding of hydrocarbons is coupled with their metabolic activation [4,5]. The ultimate metabolite of benzo(a)pyrene (BP) as suggested by Boyland [6] has been isolated as a K-region epoxide by Grover et al. [7] . Since the extent of metabolite(s) binding to DNA is very low (1 hydrocarbon molecule per 20,000 to 50,000 nucleotides), we tried to see if there is a preferential binding on certain species of DNA. Since the nuclear DNA of higher organisms contain repeated nucleotide sequences [8] that were isolated as satellite DNA’s [9-121, we studied the binding of BP metabolite(s) to main and satellite calf thymus DNA’s in vitro. It has been recently shown by Filipsky et al. [ 131 that it is possible to fractionate calf thymus DNA into a number of components by Ag+-Cs,SO, preparative density gradients. Gelboin [5] described an in vitro system in which benzo(a)pyrene, metabolized by microsomal enzymes, binds covalently with calf thymus DNA. It is shown in this report that, in vitro, benzo(a)pyrene metabolite(s) bind throughout the total calf thymus DNA and do not exhibit a preferential binding to one satellite DNA. However the data show that the BP metabolite(s) are bound to all satellite DNA’s to a higher extent than to main DNA.