Document Type

Thesis - Open Access

Award Date

1987

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. Donald P. Evenson

Abstract

Hydralazine has been used medicinally as an antihypertensive since 1952. Within two years after its introduction to clinical medicine, an unusual set of symptoms was noted in a significant portion of patients. This set of symptoms resembled those symptoms observed in idiopathic systemic lupus erythematosus. The fundamental problem underlying this drug-related systemic lupus erythematosus is autoimmune in nature. Hydralazine produces a characteristic profile of anti-nuclear antibodies that is unique from that present in idiopathic systemic lupus erythematosus. Other drugs such as procainamide and isoniazid have also been associated with drug-related systemic lupus erythematosus. Interestingly, these drugs differ in the antinuclear antibodies with which they are associated. The reason for the formation of these antinuclear antibodies is unknown. It is generally agreed that hydralazine is interacting with normal nuclear material, in particular, DNA, RNA and histones, and in some way eliciting an immune response; This response to hydralazine is a dose-related phenomena and shows a prevalence for slow acetylators; acetylation is the predominant metabolic route for hydralazine elimination. The objective of this research was to determine the relationship between hydralazine concentration and cell growth and differentiation both in vivo and in vitro. Hydralazine-induced alterations of chromatin structure of both histone containing somatic cells and protamine containing sperm cells were analyzed in an attempt to study mechanisms of these alterations that may provide clues as to why hydralazine treated patients develop antibodies against DNA/chromatin with lupus-like symptoms.

Library of Congress Subject Headings

Cell differentiation

Cells -- Growth

Hydralazine

South Dakota State University Theses

Format

application/pdf

Number of Pages

147

Publisher

South Dakota State University

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