Date of Award:

5-1994

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Ann E. Aust (Committee Chair)

Committee

Ann E. Aust

Abstract

Fibrous carcinogens, such as crocidolite asbestos, are known to catalyze many of the same reactions as iron, namely O2 consumption, generation of reduced oxygen species, and damage to DNA, such as strand breaks, and modifications of bases. Upon inhalation, fibers are also known to become coated with an iron-rich material. The mechanism by which this iron is bound to fibers in the lung is not known, and the effect of this additional iron on the reactivity of the fibers is also not well understood. The studies described here were undertaken to elucidate the abilities of crocidolite asbestos, in its native, soaked, and iron depleted forms, as well as three varieties of silicon carbide whiskers, to acquire reactive iron on their surfaces. The aim has been to quantitate the amount of iron that can bind in short periods of time, and to measure any changes in biochemical reactivity toward DNA following binding of iron. All forms of the naturally occurring mineral fiber crocidolite, and the man-made mineral fibers (silicon carbide whiskers), were capable of acquiring iron, to varying degrees. Native crocidolite was able to bind up to 57 nmol Fe+2/mg crocidolite in one hour, while the iron-depleted form was capable of binding only 5. 5 nmol Fe+2/mg crocidolite, and the three varieties of silicon carbide whiskers bound from 2.9 to 29.0 nmol Fe+2/mg in the same time period. Following iron binding, the fibers were more capable of forming DNA single-strand breaks. The increase in the ability of the fibers to cause DNA strand breaks was greatest with the silicon carbide whiskers, less with iron depleted crocidolite, and the least with native crocidolite, which is likely because of the inherently high iron content of native crocidolite. Other investigation attempted to determine whether iron could be bound from more complex, physiologically relevant iron-containing solutions where potential iron chelators are abundant. Iron appeared to be acquired even from such complex mixtures as tissue culture media. Following incubation in media, the fibers were more active in catalyzing the formation of DNA strand breaks. An interesting correlation was noted between the abilities of the fibers to cause DNA strand breaks after incubation in tissue culture media and the cytotoxicity of crocidolite to A549 cells grown in the same media.

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