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iphophorus is a freshwater fish genus comprised of 23 species. These fishes (if one refers to multiple species one uses the term "fishes") live in eastern drainages in Mexico, Guatemala, Belize and Honduras, with most of the described species living in Mexico. The taxa make up 3 groups, the Northern Swordtails, the Southern Swordtails and the Platyfish. If these names are familiar to you, there is a good chance that you have seen these fish at pet stores, as they are very popular with hobbyists.
Images of beautiful Northern Swordtails Images of glorious Southern Swordtails Images of spectacular Platyfish
t was realized as early as the 1920's that one could make hybrids between the different species. These hybrids were normally viable and could produce subsequent generations of offspring. In some cases, one simply had to place one Xiphophorus species next to another in an aquarium, and they would reproduce. In many situations, the resulting hybrid fish that were produced would show traits from both parent species, and were intermediate in appearance. For example, several dominant pigment patterns derived from two fish strains would appear within F1 hybrids, thus giving them characteristics of both species. In other cases, the hybrid fish were quite different from either parent, such as when fish developed beautiful red or yellow colors. In such situations, pigment patterns were derived from one of the species and became enhanced in the hybrid offspring. It was also realized by scientists in Germany and the United States, that hybrid fish sometimes also developed melanoma, one of deadliest skin cancers. These melanomas were derived from improperly regulated melanistic pigment patterns. Scientists immediately began to study Xiphophorus hybrids, since they realized that they had discovered an animal model that could be useful in the study of cancer.
oday, we continue the work that was begun by the scientists in the 1920's and pursued by other researchers for the last ~70 years. Our work focuses on studying melanoma that forms in hybrid fish. A genetic cross between two Xiphophorus species that leads to the development
of melanomas:
ince many of these melanomas form "spontaneously" in the absence of environmental factors such as sunlight or chemicals in the water, one can try to identify responsible genetic factors or "genes". Vertebrates such as a fish or a human contain between 60,000 and 100,000 genes that code for the "genetic information" of an individual. These genes, usally through the proteins that they code for, interact and contribute to how an organism develops, and what it looks like. We have discovered two genes are improperly regulated in hybrid fish. One gene, referred to as Xmrk-2 (Xiphophorus melanoma receptor tyrosine kinase) is related to a gene in humans called EGFR (or HER-1) and is improperly regulated within melanocytes. Melanocytes are cells that produce melanin, a group of pigments that range from browns to black. Within hybrid fish, melanocytes can proliferate uncontrollably and develop into melanomas. EGFR has been also found to be aberrantly regulated in a subset of human melanomas, further validating study of the fish animal models as being a worthwhile endeavor.
nother gene, referred to as CDKN2X maps to a genomic region implicated in melanoma tumor suppression in hybrid fish. This gene is related to a human tumor suppressor gene known as CDKN2A or P16. At this point in time, research suggests that both CDKN2X (in fish) and CDKN2A (in mammals) are performing tumor suppressive functions in melanomas.
e have also expanded the scope of our work to include study of ultraviolet radiation (UVR), often referred to as "black light".UVR, often called black light, is one of many kinds of waves that comprise the electromagnetic spectrum. Ultraviolet radiation comprises wavelenghts between visible light and x-rays on the spectrum. It consists of high-frequency wavelengths ranging from 200 nanometers to 400 nanometers, which are invisible to the human eye. UVR is further subdivided into three groups, UVA (320 to 400 nm), UVB (290 to 320 nm) and UVC (200 to 290 nm). UVB has been shown to induce sunburn, and damages DNA, the genetic material. Such damage can lead to several forms of skin cancer, including melanoma. The primary source of environmental UVR is the sun. We are shielded from much of the damaging UVR by the Earth's atmosphere with the "Ozone layer" playing a leading role absorbing these waves (particularly UVB and UVC). However, increasing amounts of UVR seems to be making its way to the Earth's surface, attributed to a depletion of ozone in the upper atmosphere due to pollutants such as "chlorofluorohydrocarbons" (CFCs). Not surprisingly, melanoma is also on the rise, corresponding to the increased UVR in our environment. We have used Xiphophorus hybrids to study how UVR can contribute to melanoma formation. We use hybrid crosses, which are already susceptible to developing melanomas, and subject them to precise amounts and types of UVR. We then compare the tumor incidence to that of "control" fish that were not subjected to UVR. The table below shows the result of one such experiment.
e have concluded from these data and other experimentation, that UVR can contribute to melanoma formation in fishes. Taken together with work from other scientists, it can be concluded that UVR certainly contributes to the increasing rise of melanoma which affects, and even kills thousands of people every year. We can minimize exposure to UVR by not staying out in direct sunlight for extended periods, or wearing sunscreens when we have to spend time outdoors. In the meanwhile, we continue to work with the small fish Xiphophorus to understand how melanoma develops, and to figure what we can do to stop it. |
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