Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are major constituents of crude oil, and the 3-5 ringed alkyl-PAHs have been identified as the main components chronically toxic to fish. While chysene homologues have higher cytochrome P4501A (CYP1A) induction potencies than alkyl-phenanthrenes, there is little characterization of toxicity for 4-ringed alkyl PAHs. This study measured the chronic toxicity of chrysene, benz[α]anthracene, and some alkylated congeners to the embryos of Japanese medaka (Oryzias latipes) using the partition-controlled delivery method (PCD) of exposure. This exposure method relies on the partitioning of chemicals from polydimethylsiloxane (PDMS) films, loaded with various concentrations of test chemical, to embryo rearing solutions. The objectives of this thesis were: (1) to further characterize the PCD method with a series of 4-ringed PAHs; (2) to evaluate the effects of different chemical structures on the toxicity of test compounds; and (3) to extend structure toxicity relationships from alkyl-phenanthrenes. The PCD method generated a gradient of aqueous concentrations for test compounds, and these exposure concentrations were maintained constant for the 17-day period. Benz[α]anthracene showed higher toxicity than chrysene. Toxicity increased with the degree of alkylation on the ring structures, except that 2-methylbenz[α]anthracene was less toxic than the unsubstituted benz[α]anthracene. Substitutions at the middle region contributed to a higher toxicity than substitutions at the distal region. While actual mechanisms for these compounds to cause toxicity are unknown, the narcotic mode of action seems to be not involved due to the lack of mortality. Within the range of test concentrations, the chronic sublethal toxicity was limited by the low solubility of the test compounds. A structure toxicity relationship was illustrated by the regression between log EC50s and log Kow values. In addition to hydrophobicity represented by log Kow, structural dissimilarities between compounds and physical characteristics such as aqueous solubility limits should be taken into account in toxicity assessments with alkyl-PAHs. This research is the first toxicological assessment of alkyl-chrysenes and benz[α]anthracenes which is essential for a better understanding of structure toxicity relationships of alkyl-PAHs, and will contribute to more accurate ecological risk assessments of PAH contamination. / Thesis (Master, Biology) -- Queen's University, 2014-01-10 16:35:00.232

Thesis (Ph. D.)--University of Chicago.

Thesis (Ph. D.)--University of Chicago.

Thesis (M.S.)--University of Wisconsin--Madison, 1964. / eContent provider-neutral record in process. Description based on print version record. Bibliography: l. 50-53.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1968. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Thesis (M.S.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Abstracted in Dissertation abstracts, v. 19 (1959) no. 8, p. 1936-1937. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 137-140).

No description available.

No description available.

Several short oligoribonucleotide sequences containing modified purine residues of biological significance were synthesized using the phosphotriester method developed in Neilson's laboratory. Variable temperature proton nuclear magnetic resonance (NMR) spectroscopy was used to examine the solution conformations of these oligomers. Studies of the effect of position, type and extent of alkyl modifications on helix structure and stability were undertaken. The triribonucleotide GpCpA was the first trimer shown to form a stable RNA duplex (Tm 33°C) (Alkema, et al, 1981(a)). This duplex contained two G:C base pairs and two 3'-dangling adenosine residues, and had a stability equal to that of the tetramer duplex UpGpCpA, having four Watson Crick base pairs. A series of GpCpN trimers was prepared (N= m⁶A, m⁶₂A, m¹G, m⁶G, e⁶G, m²m⁶G), using GpCpA as a reference, to determine how N-or O-alkylation of the dangling residue affected duplex stability. Both the studies of the N-alkylated (N=m⁶A, m⁶₂A, m¹G) (D'Andrea, et al, 1983) and 0-alkylated (N=m⁶G, e⁶G, m²m⁶G) sequences (present work) led to the conclusion that site and degree of modification were important factors for stability. Comparison of N-versus O-alkylated sequences revealed how the hydrophobic regions surrounding the alkylated nitrogen or alkylated oxygen atoms, and the spatial location of these regions, contributed to duplex stability. Examination of the effect of modified guanosine residues within a short squence, was performed through studies on ApGpNpCpU pentamers (N=m⁶G, e⁶G, m²m⁶G), having N in internal non-base-pairing and. in internal base-pairing positions. No duplex formation was seen, in contrast to studies involving reference compounds : ApGpGpCpU (a qualitative reference), ApGpGpCpU : ApGpUpCpU (Tm 31.4 C), and ApGpGpCpU : ApGpCpCpU (Tm 47.0 C). As no melting temperatures could be calculated for the modified strands, and because their NMR analyses were so similar, no comparisions regarding degree of destabilization, could be made amongst the various modified residues. Never the less, it is clear that O-alkylation of the central G residue significantly disrupts duplex formation, through generation of a centre of great instability. This result sharply contrasts that when the same modified residues are located in terminal, non-bonding positions. / Thesis / Master of Science (MSc)