Fish Offer Clues to Melanoma

 

Dr. Donald C. Morizot has been examining fish genomes in an effort to explain why some people are more susceptible than others in developing melanoma.

 

 

When he first started studying fish some 25 years ago, Dr. Donald C. Morizot had a hard time convincing many colleagues that his research was remotely related to cancer. Today, though, he has little trouble demonstrating that the fish genes he studies are more similar to human genes than even he suspected in the early 1970s - and that his findings from examining genes in many thousands of fish can help explain why some people may be susceptible to developing melanoma and possibly other forms of cancer.

 

Dr. Morizot is an associate professor of carcinogenesis at M. D. Anderson's Science Park-Research Division near Smithville, where his laboratory has been a world leader in using fish to investigate inherited cancer.

 

At the time his fish research was featured in the fall 1986 issue of Conquest, Dr. Morizot described discoveries of regulatory genes in the fish that pointed to two different mechanisms that can cause melanoma. "Both mechanisms are genetic, but in one you're dealing with a predisposition and in the other a more random phenomenon," he noted then.

 

Now a decade later, he says, "Our research has progressed quite well and is extremely satisfying, in large part because we have the sophisticated molecular tools to identify, clone and map so many genes. The most fascinating aspect of this work has been the identification of chromosomal segments that have been conserved over an estimated 450 million years of evolutionary divergence of fishes from mammals."

 

Dr. Morizot primarily has studied platyfishes and swordtails from the genus Xiphophorus. Most of them have been descendants of fish collected a half century or more ago in the rivers of eastern Mexico. These fish never mated in their natural environment, but over the years they have been artificially mated and cross-bred to produce generations of hybrid offspring with genetic features that make them good cancer research subjects.

 

Many of the inbred fish have developed a highly malignant form of melanoma due to the absence of a regulatory gene necessary for pigment cells to grow and mature. Each new generation of fish provides him with clues to help understand why some humans may be vulnerable to spontaneous melanoma as well as to melanoma caused by excessive ultraviolet radiation from the sun. One research technique involves exposing two- and three-day-old fish to heavy doses of ultraviolet light, then charting the speed with which some develop melanoma.

 

In addition to melanoma, Dr. Morizot and his collaborators analyze fish genes associated with development of other tumors, including: neuroblastoma, a cancer of the nervous system; retinoblastoma, a cancer of the eye; and rhabdomyosarcoma, a rare cancer of skeletal muscle. A new project focuses on assessment of cancer risks after the fish are zapped with various levels of ionizing radiation that mimic levels comparable to what space shuttle astronauts receive.

 

Using fish for cancer research has many advantages, such as:

· They are much less expensive than the traditional scientific studies involving mice.

· Their shorter life cycles allow investigators to collect important information faster.

· Cancer-causing compounds can be administered easily to fish tank water, which then go through the fish gills directly to organs without detoxification that might interfere with the scientific observations.

· They are ideal for melanoma studies because the usually large tumor cells show up on the outside of the fish, permitting easy monitoring as the tumors grow.

 

Currently, Dr. Morizot has approximately 200 tanks containing several generations of hybrid fish in a converted trailer nestled in the scenic wooded site where the Science Park facility is located. He collaborates with several colleagues there and at M. D. Anderson in Houston as well as with scientists in major laboratories in Germany, Japan, Canada and elsewhere in the United States.

 

His primary co-investigators include Dr. Rodney S. Nairn, an associate professor of carcinogenesis at the Science Park, and Dr. Ronald B. Walter at Southwest Texas State University in San Marcos. Drs. Morizot and Nairn collaborate on studying the relationship of ultraviolet radiation to melanoma, while Dr. Morizot works with Dr. Walter to develop new tumor models in fish.

 

Dr. Morizot is an associate director and scientific advisor for the Xiphophorus Genetic Stock Center at Southwest Texas State University. The center had been housed at the American Museum of Natural History and the New York Aquarium from its founding in 1939 until four years ago, when it was moved to Texas.

 

Fish similar to those Dr. Morizot uses at the Science Park are provided to scientists and aquarists around the world.

 

"We have more than 70 strains of swordtails and platyfishes at the center, which can breed specific hybrids for many purposes besides medical research. One reason these fish are so vital to genetic studies is the Xiphophorus gene map now is the fifth largest among vertebrates, exceeded only by maps of man, mouse, rat and cow in the number of genes assigned," Dr. Morizot says.

Return to Fall 97