Date of Award:

5-2015

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

Jeffery O. Hall

Committee

Jeffery O. Hall

Committee

Bryan L. Stegelmeier

Committee

Kevin D. Welch

Committee

Abby Benninghoff

Committee

Kerry A. Rood

Abstract

Dehydropyrrolizidine alkaloids (DHPAs) are toxins produced by approximately 3% of the world’s flowering plants that can be present naturally or as contaminants in animal feed and the human food supply. Many of these compounds have been determined to cause cancer in animals and probably also cause cancer in humans. Due to the difficulty in obtaining sufficient amounts of pure DHPAs most toxicity research has been done via injection of a small amount into the abdomen of a rodent, although natural exposure is exclusively oral. For the same reason, cancer research is limited to a handful of the hundreds of known DHPAs. The present study evaluated more sensitive animal models for both toxicity and cancer research. Toxicity of 10 different DHPA compounds was tested using male, California White chicks. Through the evaluation of blood tests, tissue tests, and microscopic analysis of organs, the selected DHPAs were grouped according to toxicity. In this model, some compounds such as heliotrine were found to be more toxic than expected based on previous research. Using this same chick model, an extract from comfrey, a commonly used herb, was found to be more toxic than either of the two major DHPAs that it contains. Because plants often contain multiple DHPAs, this suggests that the toxicity of plants, such as comfrey, may be higher than previously estimated. A mouse strain that is genetically susceptible to cancer (heterozygous p53 knockout) was tested and compared to previous studies using the same carcinogenic DHPA (riddelliine). The most common type of cancer was hemangiosarcoma (cancer of blood vessels) of the liver. These results were similar to previous studies using substantially less pure DHPA, indicating the benefit of this model to test the cancer causing potential of other DHPAs. Additionally, it was also determined that exposure to DHPAs for only two weeks (compared to years) also increased the odds of developing cancer.

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Included in

Chemistry Commons

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