The non-random covalent binding to DNA by the intercalators 8-azido-ethidium, 7-azido-actinomycin D, anti-(+)-benzo (a) pyrene 7,8-diol 9,10-epoxide, and anti-($-$)-benzo (a) pyrene 7,8-diol 9,10-epoxide was investigated using techniques analogous to DNA sequencing. A computer-assisted methodology was subsequently developed that allowed the characterization of all sequence preferences of covalent binding up to the quartet level. All intercalators exhibited some preferences in binding. 7-azido-actinomycin D was most sequence selective and 8-azido-ethidium was least sequence selective. Next-nearest neighboring bases exert a major influence on the reactivities of the intercalators. The magnitude of the next-nearest neighbor influence is almost as great as the nearest-neighbor influence. There were certain sequence preferences of covalent binding shared by all intercalators. The sequence preference analysis indicated that 7-azido-actinomycin D and 8-azido-ethidium were excellent probes for evaluating the reversible binding of the parent actinomycin D and ethidium molecules. There were some differences in the sequence preferences of covalent binding by the two benzo (a) pyrene diol epoxide enantiomers. The potent carcinogenicity of the anti-(+)-isomer may be caused by the adduct at the exocyclic amine of guanine bases, since this isomer forms more of these adducts than the anti-($-$)-isomer. / Source: Dissertation Abstracts International, Volume: 51-07, Section: B, page: 3284. / Major Professor: Randolph L. Rill. / Thesis (Ph.D.)--The Florida State University, 1990.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_78279 |
| Contributors | Marsch, Glenn Alan., Florida State University |
| Source Sets | Florida State University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | 366 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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