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Abstract: The article describes some of the scientific research that is being carried out at the University of Sydney into the effects of ozone depletion. In particular it covers the human health effects of exposure to ultraviolet light, the various ways scientists are studying these effects, the problems that they encounter in their work, and the preventative measures that they are examining.
Skin cancer has reached epidemic proportions in Australia. Two out of three Australians will get some form of skin cancer in their life times and one out of 60 will develop the potentially fatal melanoma skin cancer. The cost to the community is currently estimated to be $200-400 million per year. With depletion of the ozone layer these figures are expected to get worse. Also the costs to agriculture of animal skin cancers will increase.
Australian researchers are finding that existing assumptions about the response of animals and humans to ultraviolet (UV) light may be too crude to ensure that protective strategies are effective. Sunscreens have been developed to filter out light from the portion of the sunlight spectrum that causes sunburn, however the effectiveness of existing sunscreens in preventing skin cancer and immune suppression and the consequences of long-term use of sunscreen chemicals are still being investigated.
UV light causes some suppression of the immune system and increases the infectivity of herpes virus and of candida and increased abscess formation in mice. Dr Peter Hersey, from the University of Newcastle, has done studies of humans using sunbeds and artificial UV radiation in suntan parlours and found the same reaction in humans. People who are susceptible to cold sores and who are exposed to quite small exposures of sunlight (too small to get sunburn) can erupt in cold sores 2 or 3 days later because of the temporary suppression of their immunity against the herpes virus.
Scientists still do not know how much impact UV light has on the human immune system. In animals this immune suppression is necessary for the development of cancers. With depletion of the ozone layer more of the UV wavelengths that suppress the immune system are going to be reaching Australians. So immune suppression from exposure to sunlight is likely to become even more dangerous than the initial production of skin cancer cells.
DO SUNSCREENS WORK?
Vivienne Reeve, a researcher in Veterinary Pathology at the University of Sydney, studied the ability of sunscreens to protect against suppression of immunity caused by UV light. She and other researchers at the University use a colony mutant hairless mice as models for the development of skin cancer in humans. The mice are exposed to an artificial solar simulator with a spectrum similar to sunlight for 10 minutes, 5 days per week for ten weeks. The dose is not enough to cause sunburn but produces a slightly pink colour on the skin. Even this amount of exposure is enough to induce protective responses and the dose is increased by 20% each week. After 10 weeks the exposure ceases and the mice begin to get tumours. Ninety to one hundred per cent of the mice get skin cancer within 12 months.
Reeve has examined two different types of sunscreens by painting them on to the mice before exposing them to the artificial light. She found that whilst one, whose major active ingredient was an esther of cinnamate, was totally protective against immune suppression the other, whose major active ingredient was an esther of octile para amino benzoic acid (PABA), totally failed to protect. Both prevented sunburn equally well and she is currently investigating their comparative protectiveness from skin cancer.
UV light can also initiate skin cancer at the same time that it is interfering with the immune response and this compounds the problem. Reeve has found that although the major sunscreens on the market are very efficient in protecting the skin from sunburn and skin cancer outgrowth they do not seem to prevent the initiation of skin cancer. Potential cancer cells are still produced in the mice despite the presence of a sunscreen although the sunscreen seems to prevent the cancers from developing as fast as they would if the mouse was unprotected.
Reeve does not believe the cinnamate based sunscreen is the ideal sunscreen despite its ability to protect against immune suppression and is awaiting better sunscreens from the industry. One problem that the cinnamate sunscreen has had in the past was that 10 years ago the School of Public Health and Tropical Medicine at the University of Sydney discovered that some batches were contaminated with a mutagen and it now has to be batch tested to ensure the problem is not repeated. She believes there is a real need for watchdog organisations to monitor the products of the sunscreen industry, which after all is a multi-million dollar business. "If you are going to slather your body, your hair and your make-up with sunscreen containing topical substances, you have to be absolutely certain that they are safe and that they are protecting you."
Robert Baker, from the University of Technology, agrees. He does not believe the government has adequately evaluated the safety of sunscreens. He points out that between 10 and 20% of sunscreens spread on the skin are absorbed. Apart from the possibility that the sunscreens could cause cancer themselves he argues that "we don't know anything about the effects of the chemicals absorbed on the nervous system, liver or other organs."
One way of avoiding sunscreens is to wear more clothes, but not all fabrics are equally protective. Unfortunately it is the heavier, warmer fabrics that provide the best protection, not what fair-skinned Australians are happy to wear on a sizzling summer's day. Paul Walker, Phil Lukens and Scott Menzies from the University of Sydney have been working with Gavin Greenoak and Jules Martin of the Australian Photobiology Testing Facility and Michael Pailthorpe at the University of NSW to develop a light, cool fabric that will provide maximum protection from UV light.
The first step in this project has been to work out a way of characterising fabrics to indicate their protection factors (like a sunscreen has a sun protection factor). Measurement of a fabric protection factor is relatively straightforward and in done in the same way that sunscreens are tested. A person's skin is tested without any protection to see how long it takes for a particular dose of UV light to cause a slight pinkening of the skin. Then they are exposed to see how long it will take to cause that same pinkening through the fabric. If it takes ten times longer then that fabric is given a fabric protection factor of 10.
The trouble is that this method is time consuming and expensive and it would be better to establish a fabric protection factor without human testing, based on the geometry and transmission characteristics of the fabric. However Walker and his team have found that there is no simple relationship between the characteristics of the fabric and the human testing results, although many researchers have assumed there is.
Gavin Greenoak has been studying the role of natural tanning in protection from UV light. Greenoak, who is remarkably tanned himself, argues that although the tan offers some protection against skin damage there is really no such thing as a safe tan. "In so far as you need UV light, a known carcinogen, to induce a tan, the presence of a tan merely shows how much UV you have had." The ideal would be to produce a tan (natural pigmentation), which would offer some protection, without exposure to UV light and Greenoak is studying a substance (Melanocyte Stimulating Hormone) that he hopes might achieve this. The researchers at Sydney University have bred a mouse that develops a tan when exposed to UV light. Greenoak believes this may be the first and only tanning mouse in the world. Reeve points out that they weren't aiming for a tanning mouse. "When we first saw these different coloured pups in the litters we thought: •how cute that little beige mouse is. Lets breed that one up.' Later we discovered that they produced these wonderful tans whereas the others didn't tan at all."
TAKING ADVANTAGE OF CHANCE EVENTS
According to Greenoak, the great advantage of Australian science is that it is small. Researchers work in small groups that have to do everything from breeding the mice and feeding them to experimenting on them and killing them. Researchers in large teams in other countries do not have close contact with their animals and the people who look after the animals. "They just monitor the results they want, within fairly strict parameters, and many observations are lost. Australian researchers are in a unique position to notice the unpredicted, serendipidous event that inspires a whole avenue of research and discovery."
A few years ago researchers at Sydney University noticed a hairy mouse in the colony of inbred hairless mice. This mouse got very big and very fat and they named him Jimmy, The Elephant Mouse. More hairy mice were bred from Jimmy and Greenoak's team shaved these hairy mice and found that they were completely immune to skin cancer when they were irradiated with UV light. Chris Moran in the Genetic Section of Animal Science at the same university guessed that the hairless mouse had resulted from the insertion of genetic information (in the form of a retrovirus) into the genome of the mouse. This retrovirus must have suddenly jumped out leaving a hairy mouse. Researchers in Boston confirmed this theory. No-one knows where this retrovirus came from.
Greenoak and Moran are now working on the implications of this discovery with researchers in Boston and at the National Institute of Medical Research in London. The retroviral insertion allows the researchers to locate the hairless gene and find out what it is coding for and this may tell them something about why hairless mice are more susceptible to skin cancer than shaved hairy mice. The reason may be a physical one to do with the development of hair follicles or it may be that the hairless gene causes a deficiency in the production of a protein or secretion that is necessary for the hair to grow.
Greenoak postulates that if there is a gene in the hairy mouse that is producing something protective then there may be a possibility of inserting it, using genetic engineering, into farm animals to give them protection. UV irradiation and the resultant skin cancer are a problem with sheep, especially with tail docking when the vulva is exposed to sunlight. Cattle also get skin cancers and carcinomas of the eye. The udders of cows and goats are also susceptible. All these problems cause significant economic costs to Australia's agricultural industry as well as suffering to the animals.
Greenoak thinks it unlikely that scientists would genetically engineer humans in this way but "if this gene produces a protective substance and if mouse skin is like human skin then this product could be manufactured and used." This question of how valid it is to extrapolate results found in mice to humans is one of the major problems facing those using animal models. Vivienne Reeve says "Extrapolating from animal tests is a continual, endless problem. We can only guess, that is all we can do." She points out that ability of sunscreens to protect humans from sunburn matches their ability to protect mice from sunburn. Additionally the biochemical changes that occur in the skin seem to be the same for mice and humans.
TRANSFERRING RESULTS TO HUMANS
Another problem with using animal models is the ethical issue of experimenting on animals. Yet the researchers argue that there is no other way since you cannot experiment on humans and they point out that the work they are doing is vital for human health. "It is cruel to the mice" admits Reeve, "but we terminate every experiment before the mouse is debilitated in any way at all. We are conscious of this." Reeve believes that the problem of working with animals has made this sort of work unpopular. Apart from the pressures from animal rights groups, experiments have become very expensive because of restrictions on how they are carried out and the conditions under which the animals are housed. "Also to have to wait 12 months for an answer to your hypothesis is a long time and these days when scientists have to publish or perish it has become quite an unpopular route for a research career."
Rebecca Mason, a researcher in the Department of Physiology at the University of Sydney, overcomes the need to use an animal model by culturing skin cells in the laboratory. She is studying natural adaptive responses to ultra-violet light. Such responses include an increase in the number of pigment cells and increased dispersion of pigment leading to a tan and increased skin thickness that may protect the deeper tissues of the body. Mason, like Greenoak, is aiming to find ways to stimulate the skins protective response without the need for sun damage to occur first. She is hoping to identify some of the chemical messengers that cause the skin to thicken and tan.
Mason and her postgraduate student Nalini Dissanayake, working with St Vincent's Medical Institute of Research in Melbourne, have found that when skin cells are exposed to UV light they produce substances that cause tanning and thickening even in cells that have not been exposed to UV light. Their work is now to find out what these substances are.
Mason's ultimate aim is to find some sort of drug that people could take or cream that they could apply to the skin that would provide protection from the damaging effects of the sun. She is well aware of the commercial opportunities that could open up if her research is successful and she has already been approached by cosmetic companies. At this early stage in her research, however, she prefers to maintain her independence and be free to publish as she likes.
Bill McCarthy, from the Melanoma Unit at Royal Prince Alfred Hospital in Sydney, avoids the need for animal experimentation by directly studying people. He is currently doing a study of hundreds of children to find out more about the relationship between UV light and melanoma, which is a fatal form of cancer. Working on the basis that the number of moles a person has is strongly correlated to their likelihood of getting a melanoma, McCarthy and his team are counting moles on children in various parts of Australia where the UV light is of different intensity. The children are in Melbourne, Sydney and Townsville and are in four different age groups (6,9,12 and 15 years old). The children chosen for this study are all white Anglo-Saxons because of their susceptibility to melanomas.
The children are monitoring their own exposure to the sun with questionnaires and clip on UV monitors. At the same time UV light meters have been set up on roofs in each city close to where the schools are. The aim is to establish dose-response relationships by finding how much UV the children are exposed to in relation to the overall dose hitting the area they live in and then correlating this with how many moles they have. McCarthy hopes he will be able to study the children every three years but this will depend on the availability of funds.
Already the results are significant. Children in Townsville in Northern Queensland have six times more moles than children in Melbourne. Moles are a better indicator of melanoma potential than skin colour, eye colour, hair colour or even how the skin responds to sunlight. The early findings therefore confirm the relationship between melanoma susceptibility and intensity of UV light exposure at an early age.
McCarthy points out that children are not getting the message about the dangers of sunbaking. "People don't worry about skin damage till they are about 25 or 30 when their skin starts to look a bit damaged and a tan isn't so important any more. In terms of exposure to sunlight, once you get to the age of 25 the bulk of the damage has been done." He hopes that by providing actual evidence of childhood damage then people, particularly parents who tend to be protective of their children, will realise that their children need to be appropriately clothed or protected when they are outdoors.
McCarthy takes his responsibilities as a cancer expert very seriously and despite his busy schedule as university professor, researcher, hospital administrator and practising surgeon he still finds time to speak to public meetings. "I have a responsibility to tell the public. My status and prestige make me a good role model; I am someone whom people will listen to."
Reeve also feels the responsibility to publicise her results, even where they may offend the powerful sunscreens and cosmetics industry. She believes public pressure is sometimes necessary to achieve the necessary reforms to that industry. "I am often criticised by other scientists for going to the media but I feel quite strongly that I am doing research with public money and I am obliged to tell people about it."
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