Spectroscopic studies of DNA complexes formed after reaction with anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide enantiomers of different carcinogenic potency.

Abstract

Light absorption, fluorescence and linear dichroism (l.d.) spectroscopy and fluorescence lifetime measurements reveal characteristic differences that arise from structural differences between the DNA complexes with the optical enantiomers (+)- and (-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides (BPDE), a strong and a weak carcinogen, respectively. Both types of complexes appear heterogeneous but can be described as composed of two major complex types I and II, in different proportions. Like previously observed for DNA modified by racemic anti-BPDE, the only distinguishable spectral component of (+)-anti-BPDE-DNA is the type II complex, whereas the (-)-anti-BPDE-DNA is a mixture of both types I and II complexes. The type I complex is characterized by negative I.d., a light absorption and excitation spectrum maximum (above 300 nm) at 354 nm and strong fluorescence quenching in native DNA, properties expected for an intercalation complex in the classical sense. The type II complex on the other hand is characterized by positive I.d., a light absorption and excitation spectrum maximum (above 300 nm) at 345 nm, and moderate fluorescence quenching in native DNA, properties not consistent with intercalation geometry. Rather, the BPDE chromophore forms less than 55 degree angle with the mean direction of the helix axis. Its interaction with the DNA bases seems to be less than in complex I, and is highly sensitive to Ag+ ions. The type II complex may be associated with local obstruction of base-pairing properties of native DNA. Since DNA-binding of chemical carcinogens is considered crucial for tumour initiation it follows that the unique properties of the type II BPDE-DNA complex may be of fundamental importance in benzo[a]pyrene carcinogenesis.