Professor leads research to identify cancer preventive drugs

Photos by Irvin S. Cardenas.

Irvin S. Cardenas/Contributing Writer

Arsenic, a known carcinogen, is almost unavoidable by humans. Traces of it can be found in rice, drinking water, apple juice and even in chicken meat.

However, Barry Rosen, associate dean of basic research and graduate programs, said that although finding arsenic in our poultry sounds frightening, we should not be scared.

Rosen is a molecular biologist that has been studying arsenic for over 30 years.  Rosen and a team of researchers have made discoveries ranging from new genes, enzymes and pathways that are involved in the creation of arsenic-related cancer.

Rosen’s latest research focuses on the analysis of arsenic in microorganisms.

[pullquote]“One of the biggest risks with arsenic is that it causes cancer in humans,” said Rosen.[/pullquote]

To tackle the issue of arsenic-related cancer, Rosen and his team are coming up with ideas about the development of drugs that could prevent “arsenic carcinogenesis,” or the creation of arsenic-related cancer.

Rosen was recently awarded a $100,000 grant by Florida’s Department of Health for his proposal titled “Development of high-throughput assays to identify drugs to prevent arsenic carcinogenesis.”

His research will investigate large-scale procedures, or screenings, to assess enzymes and chemical compounds as possible drug components

“If you can do one thing at a time, it takes you a long time to get anything done. But if you can do them typically in the types of assays that we do in our laboratory, using 96 well plates, then that means doing 96 assays at the same time,” said Rosen.

Dr. Rosen Photo Discussing Arsenic in RiceWith the one-year grant, Rosen and his team will research the developmental process of these highly desired drugs.

“We feel that within this year we should be able to develop the tools, the assays, that we need to be able to screen for drugs,” said Rosen.

Rosen said that their initial goal for this research is not to identify the drugs, but to create the tools needed to screen for the drugs.

An analogy, Rosen said, would be that they are not building cars, but rather making the tools that will be used to build cars.

He said that the task of this research is to develop a process where they can see arsenic methylation in real-time. In our bodies, the progress of arsenic causing cancer begins when the arsenic is taken into the liver and a liver-residing enzyme transforms it into this carcinogen.

Current assays that model this process can take days and are not suitable for identifying compounds that are possible drug candidates.

The novelty of this initial research involves finding a way to see the enzymatic process in seconds or minutes, rather than hours or days.

Rosen can’t mention what the finalized version of these assays will look like yet. But to give us a better idea, Rosen said that it will be an adaptation of a procedure they are developing. In this assay they have enhanced the ability to emit fluorescence of an enzyme called methyltranferase. This assay has demonstrated that arsenic binding to this enzyme causes a large change in fluorescence in milliseconds.

“We will adapt this assay to look for potential drugs that can prevent arsenic binding to the enzyme,” said Rosen.

Rosen said that after achieving such assays using a high throughput process, typically using their laboratory equipment of 96 well plates, they could collaborate with other facilities, such as Torrey Pines Institute for Molecular Research, which performs this process on a very large scale.

“These facilities also have more potential drug compounds that we can test,” said Rosen.

Research states that arsenic is the most ubiquitous toxin and carcinogen endangering human health.

[pullquote]“Long-term exposure through an increase of arsenic in our diet, or direct contact with inorganic arsenic, can cause major health problems leading to skin, bladder, or lung cancer,” said Rosen.[/pullquote]

Further evidence of its danger can be seen in the Agency for Toxic Substances and Disease Registry’s “U.S Priority List of Hazardous Substances,” which ranks arsenic as number one.

Rosen said that while arsenic is linked to these cancers, arsenic-related cancer is usually associated with geological formations. This is the case of locations such as West Bengal, India, where there are high levels of arsenic in the Ganges River or in Chile and other South American countries where a lot of the arsenic is found associated with copper and silver mines.

As far as the issue of arsenic in our diet goes, Rosen believes that we should be mostly concerned with rice, especially since recent discoveries show that rice is a natural accumulator of arsenic.

During a discussion of their recent discovery of a structure involving roxarsone, an industrially made arsenic-bonded compound, Rosen reiterated his point.

“I think Rice is the problem, not apples or chicken,” said Rosen after a comment from Charles Packianathan, a research associate from the Department of Cellular Biology and Pharmacology.

Packianathan said that roxarsone is often used as a feed additive for chickens to increase their weight, as illustrated in his research.

The team’s research has led them to pioneer the process of genetically engineering rice that could naturally vaporize arsenic.

It is this sort of research that has led to various arsenic-related discoveries, and to his pursuit of finding arsenic-preventing drugs.

There are currently no assays to identify drugs that prevent arsenic carcinogenesis; Rosen and his team of researchers would be the first to achieve this.


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