Base sequence effects on interactions of aromatic mutagens with DNA (deoxyribonucleic acid)
Year: 1989
Type: report
Abstract: The base-sequence dependence of the adduct conformations-derived from the covalent binding of trans-7,8-diol-anti-9,10--epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) (+) and (-) enantiomers to synthetic DNAs of defined base composition and sequence is described. The diol epoxide BPDE is the ultimate mutagenic and tumorigenic metabolite of benzo(a)pyrene, a common air pollutant, which is a byproduct of fossil fuel combustion processes. The covalent addition products of BPDE can be classified according to two types: (1) site I, involving carcinogen-DNA base stacking interactions, and (2) site II, in which the BPDE residue appears to be located at a partially external DNA binding site. The presence of site II adducts, rather than site I adducts, is correlated with high mutagenicities and tumorigenicities of polycyclic aromatic diol epoxides. It is shown here that the formation of site II adducts derived from the binding of the more tumorigenic (+)- BPDE enantiomer to DNA is particularly favored in deoxyguanine-rich sequences. 12 refs., 6 figs., 3 tabs.
DOI: 10.2172/5643342
Author: N. Geacintov
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3209274648