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The impact of energy related pollutants on chromosome structure

Technical Report ·
DOI:https://doi.org/10.2172/5345926· OSTI ID:5345926

The sequence preferences of DNA binding by five intercalating chemicals were examined by techniques analogous to chemical DNA sequencing. The intercalators used were 7R, 8S-dihydroxy-9S, 10R-epoxy-7, 8, 9, 10-tetrahydrobenzo(a)pyrene (anti-(+)-BPDE) and its enantiomer, anti-({minus})-BPDE; 8-azido-ethidium, 7-azido-actinomycin D, and bis-(1, 10-phenanthroline)Cu(I). The former four compounds form covalent adducts, some fraction of which are labile and cause DNA chain cleavage upon treatment with hot piperidine. The latter compound causes spontaneous chain cleavage via activated oxygen species generated in the presence of molecular oxygen and a reducing agent. Quantitative mapping data on the DNA cleavages caused by these chemicals were obtained on over 1200 DNA bases in restriction fragments and were statistically analyzed. The sequence preferences of all compounds were best described in terms of base triplets, but bases flanking the preferred triplets also influenced binding in many cases. Although the intercalators differed in degree of sequence selectivity and triplet sequences most preferred, YRY and YGG sequences were generally preferred, especially when the 5'-Y was T, while RRY and oligo-purine/oligo-pyrimidine tracts were generally avoided. Details of individual intercalator preferences and other features of the DNA binding of these compounds are described. 17 refs.

Research Organization:
Florida State Univ., Tallahassee, FL (USA). Inst. of Molecular Biophysics
Sponsoring Organization:
DOE/ER
DOE Contract Number:
FG05-87ER60588
OSTI ID:
5345926
Report Number(s):
DOE/ER/60588-3; ON: DE90002541
Country of Publication:
United States
Language:
English