The Hole Story:
The Mouse Model of Cancer ctd.
Immunity and Skin Cancer
The basic aim of Scott Menzies' research is to look at the reaction of the immune system to UV light and the role of this reaction in the cause of skin cancer. To do this he has developed a special type of tumour which will only grow on mice that have had their immune system suppressed by UV light. The basic test to determine whether or not UV light has caused immune suppression involves two groups of mice. One group is given a whole body dose of UV for 7 weeks that is not enough to cause cancer. The other is not irradiated at all. The irradiated mice are then injected with the tumour, which almost always grows in these mice, no matter how long it is after they have been exposed to the UV light. But when the tumour is injected into the other group of mice that have not been irradiated the tumour never grows.
At the same time Menzies has also been inducing skin cancer in mice without immune suppression. He has been doing this by repeatedly irradiating only a very small region of a mouse, 0.8cm square. By irradiating a very small area the dose per unit area is quite high, high enough to induce a skin cancer, but the total dose per square centimetre of the animal is very low. In this way he can avoid suppressing their immune systems yet induce skin cancer. He excises these skin cancers, determines they are in fact skin cancers, and then injects the tumour line to see whether it will grow. It never does says Menzies, and this proves there is no immune suppression in these mice although they had developed skin cancers. He supposes that the reason the mice do not have their immune systems suppressed, even though they are being exposed to UV light, is simply because the area of exposure is so limited, but he's not sure.
There was a theory published in the journal Science that says the UV suppression of the immune system is necessary for skin cancers to exist, says Menzies. I am questioning this theory by examining the corollary of this hypothesis. This is that you can't induce skin cancer without that immune suppression existing. What I have shown is that you can induce skin cancer without the immune suppression of the system. This question is very important because it has a bearing on whether you could have successful immunisation programs against skin cancer.
Menzies is testing for suppression of the whole immune system and he admits it is possible that in the local area of irradiation there could be immune suppression. It has been reported in the literature that there may sometimes exist a local immune suppression as opposed to systemic immune suppression. However, he points out that a recent paper has also suggested that local and systemic immune suppression are probably the same thing.
He can't validly test for local immune suppression because he would need to inject the tumours very high up in the skin which is impossible to do with the number of cells he uses. Also he would have to keep repeatedly injecting because local immune suppression is short lived. Systemic immune suppression is a long lived phenomenon and he can wait and inject at any time to see whether it exists or not. Local immune suppression on the other hand may wax and wane and go away so it may be virtually impossible to pick the correct time to inject. For these reasons he has found local immune suppression to be virtually untestable for tumour work.
It has been shown that UV light also immune suppresses mice for infectious diseases as well as skin cancer. This has been done with Herpes simplex virus, the cold sore virus, and also the type 2 genital Herpes viruses. Mice can also be immune suppressed for certain parasitic infections. This can all be done with doses of UV that are too small to induce skin cancers.
Having intense UV light on your hands and neck alone could produce immuno-supression. says Menzies. Mice have developed immuno- suppression just by having their tails irradiated. Certainly a person could still get tumours from having a small amount of skin exposed. It is well known that there are more skin cancers on the right arms of men than on their left arms because of the common habit of driving with the right arm hanging out the window. Remember that UV is a carcinogen. It will mutate cells and that is the reason that skin cancer occurs.
All this means that when someone is exposed to the sun, even if they are wearing a T-shirt so only their arms are exposed, they might become immune suppressed everywhere. In mice this immune suppression lasts for the lifetime of the animal. So if a person gets enough sun to become immune suppressed it could last a long time, perhaps even a life-time. No one knows for certain how much sun it would require to suppress the human immune system. It is difficult to determine. Human immuno-suppression has not been looked at adequately because it is not possible to carry out the necessary irradiation experiments.
Menzies does not support research into a vaccine against skin cancer because a vaccine helps the the immune system to work and he doesn't think that the immune system plays much of a role in preventing skin cancer. But there are problems extrapolating his study from mice to humans. First of all the immune systems are different. There are some types of immune cells that exist in mice that don't exist in humans, particularly in the skin. Also observations in mice are different in humans.
Mice do not have something called the photoreactivating enzyme. This is a phenomenon detected in certain other mammals. It is questionable whether humans actually have it but we know mice don't have it. Mice are nocturnal and they are also usually hairy, so it is not surprising that they don't have the photoreactivating enzyme. Being active at night and having lots of hair has resulted in evolutionary constraints not requiring it for survival. So mice are not the best animal model for humans, but they have got some advantages. .