Igor Mrdjen, a PhD student in the College of Public Health’s Division of Environmental Health Sciences, has received the Science Communication Award at the International Association for Great Lakes Research’s 60th Annual Great Lakes Research Conference, held in Detroit in May.
Mrdjen’s research, titled “Evaluation of Cyanobacteria and Their Toxins in a Two-staged Model of Hepatocarcinogenesis,” showed that chronic ingestion of the toxins may promote the development of liver tumors in mice previously exposed to a chemical carcinogen. The study was co-authored by CPH faculty members Jiyoung Lee, PhD; Thomas Knobloch, PhD; and Christopher Weghorst, PhD.
The research focused on the toxins that can be created during harmful algae blooms in which cyanobacteria, microscopic organisms found in most lakes and rivers, grow rapidly and affect the cleanliness of the water.
“The cyanotoxin we tested was Microcystin-LR (MC-LR), the most prevalent toxin found in Lake Erie, Grand St. Mary’s, and Buckeye Lake, and the most potent toxin of the Microcystin family,” Mrdjen said. “MC-LR has been cited as a suspected carcinogen by the International Agency for Research on Cancer and can produce negative outcomes in acute exposures. In the past, Toledo has had to shut down its water supply due to these toxins.”
“This pilot study substantiates the need for additional research to be done, not only to further define the cancer-causing potential of these toxins in preclinical animal models, but also to translate these findings to humans and other mammals in an effort to best prevent negative outcomes from occurring.”
The pilot experiment tested whether ingesting low concentrations of MC-LR in drinking water over a long period of time (30 weeks) would accelerate the progression of liver cancer development in mice previously exposed to a liver carcinogen. Additionally, Mrdjen tested if the ingestion of cyanobacterial cells containing multiple Microcystin toxins would promote the progression of tumors to an even greater extent.
“We used a different model of exposure, treating mice first with a chemical to start the cancer process and then allowing mice to drink the toxin or bacteria-laced water freely, without relying on gavage or injection techniques,” Mrdjen said. “This type of exposure to cyanobacterial cells would be equivalent to recreational exposures, or consumption of untreated water often seen in developing nations.”
Based on the results of the experiment, Mrdjen was able to observe that while mice exposed to MC-LR or the cyanobacterial cells at low doses in their drinking water for 30 weeks did not develop significantly higher numbers of tumors than the mice drinking clean water, the tumors that did form were more advanced, which Mrdjen said suggests that Microcystin toxins may be acting as liver cancer promoters in mice.
“Additionally, we found that the toxicity of ingesting a cyanobacterial mass with equivalent MC-LR concentrations produced a significantly higher death rate in the mice, hinting that some combinatorial effects due to the presence of multiple toxins may be a factor in the health of the mice,” Mrdjen said.
Mrdjen’s presentation was not only recognized for the content of his research, but for the communication of his findings in a way that was clear and understandable.
“The challenges [of this presentation] were trying to explain the process of carcinogenesis and tumor promotion in a way that is easy to understand, yet is accurate,” Mrdjen said. “I used analogies often used by my professors to explain it plainly to audiences which are not familiar with the topic. Most commonly, I reference a car analogy; where the initiation of a cancer cell by a chemical is the key turning the car on and the process of increasing the proliferation of that initiated cell is determined by the amount the gas pedal is depressed, allowing the car to move forward (tumor development). Some environmental exposures push the gas pedal down more than others. If the gas pedal is applied too powerfully or progressively applied for too long a period of time, the car can go out of control and crash…malignancy.”
According to Mrdjen, this project impacts the environmental health sciences community by expanding the body of evidence associated with this highly relevant topic utilizing the unique combination of a two-stage cancer model, a liver cancer-sensitive mouse, and an exposure approach that represents real world exposures, to investigate of the role of Microcystin toxins as potential tumor promoters.
“This pilot study substantiates the need for additional research to be done, not only to further define the cancer-causing potential of these toxins in preclinical animal models, but also to translate these findings to humans and other mammals in an effort to best prevent negative outcomes from occurring,” Mrdjen said.
Mrdjen’s faculty advisers were integral components of this interdisciplinary research study. Lee specializes in cyanobacteria and serves as Mrdjen’s academic advisor, while Knobloch and Weghorst specialize in carcinogenesis.