Published in the journal "Carcinogenesis", one study found that female mice that had 24-hour access to running wheels and were exposed to ultraviolet B light (UVB) took longer to develop skin tumours, developed fewer and smaller tumours, and had decreased amounts of body fat compared to mice that did not have access to running wheels. The second study looked at the development of pre-cancerous polyps in the intestines of male mice and discovered that voluntary exercise and a restricted diet reduced the number and size of polyps and improved survival.
Dr Allan Conney, Garbe Professor of Cancer and Leukemia Research and Director of the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers University, New Jersey, USA, is one of the authors of the skin cancer study. He said that programmed cell death (apoptosis), triggered by exercise, might explain why the running wheel mice did better.
"Preliminary indications from follow-up work in the laboratory suggest that voluntary exercise enhances UVB-induced apoptosis in the skin, and that it also enhances apoptosis in UVB-induced tumours. So, although UVB is triggering the development of tumours, exercise is counteracting the effect by stimulating the death of the developing cancer cells.
"Our studies may be the first to suggest an apoptotic mechanism for the effect of voluntary exercise in the development of cancer. In addition, we found that voluntary exercise decreased body fat and that the number of tumours decreased with decreasing amounts of fat. This effect may also play an important role in the mechanism and warrants further investigation, bearing in mind the growing rates of obesity in the Western world, particularly in the USA and UK," he said.
Dr Lisa Colbert, Assistant Professor at the University of Wisconsin-Madison, USA, lead author of the bowel cancer study, said that her study was the first to suggest that a negative energy balance, produced by increasing the mice's energy output (by use of a running wheel) while maintaining a restricted calorie intake, appeared to be the important factor in inhibiting the growth of polyps (the fore-runners of bowel tumours).
"Negative energy balance was indicated by a lower body weight among the exercising mice, although they retained more body fat at the end of the study than the non-exercising mice – an observation that might be due to the fact that the exercising mice were healthier, while the health of the non-exercising mice was beginning to decline due to higher numbers of polyps. There were higher levels of hormones known to be associated with the onset of cancer – insulin-like growth factor-1 (IGF-1) and corticosterone – amongst the exercising mice, but this did not correlate with higher total polyp numbers. These data suggest that voluntary exercise that induces a negative energy balance protects against the onset of cancer in these mice, but that the mechanism is unlikely to be related to body composition, IGF-1 or corticosterone."
Dr Conney emphasised that it was not known yet whether exercise decreased the risk of sunlight-induced skin cancer in humans, and clinical trials were needed to investigate this further. However, in bowel cancer, evidence from population studies already suggests that physically active people have a reduced risk of developing the disease, but the mechanisms remain unclear.
The skin cancer study involved two experiments. In a "high risk" model, mice were exposed to UVB three times a week for 16 weeks, and then for the subsequent 14 weeks, in the absence of further UVB treatment, half the mice had access to running wheels in their cages while the other half did not. In a second, "complete carcinogenesis" model, mice were exposed to UVB twice a week for 33 weeks and, from the beginning, half had access to a running wheel and half did not. Mice not exposed to UVB acted as controls for the study. In both models, the exercising mice increased their food intake and maintained their normal body weight.
The exercising mice in the high risk model had an average of seven weeks without tumours after the UVB exposure ceased, while the non-exercising mice only had an average of 3.5 tumour-free weeks.
Dr Conney said: "In both the no running wheel and running wheel groups, the number of tumours per mouse increased with time, but throughout the 14 weeks of tumour development, animals with access to running wheels had a decreased number of tumours per mouse compared to animals with no running wheels. At all times, the tumour size in the no running wheel group was greater than in the running wheel group; on average, the tumour size per mouse for the no wheel group was just over three times more than for the exercise group."
In the complete carcinogenesis model, mice with no running wheel started to develop tumours 20 weeks after the start of UVB exposure, while tumours in the running wheel group started after 23 weeks. The average tumour-free time was 25 weeks for the no running wheel group and 27 weeks for the running wheel group.
Dr Conney said: "The rate of increase in tumour numbers per mouse for the no running wheel group was significantly greater than that for the running wheel group. On average, the tumour size per mouse for the no running wheel group was about 3.5 times more than in the exercise group.
"In both models, voluntary running decreased the number of non-malignant tumours per mouse by 34%. Exercise substantially decreased the size of non-malignant tumours and malignant tumours: in the high risk model, the non-malignant tumour size per mouse was decreased by 54% and the malignant tumour size per mouse by 73%, and in the complete carcinogenesis model, tumour size per mouse was decreased by 75% and 69% respectively."
For the bowel cancer study, Dr Colbert and her co-authors used mice (APC Min mice) that had a genetic mutation that predisposed them to develop intestinal polyps. "Our studies are relevant for humans in that these Min mice have a mutation in one of the same genes, APC, that is also mutated in human colon cancer," she explained. "The protective effect of exercise and lower body weight in our mice is consistent with epidemiological evidence in humans that suggests higher levels of activity and lower body weight reduces the risk of colon cancer."
Mutations in the APC gene in humans are responsible for an inherited condition called familial adenomatous polyposis (FAP). FAP affects about one in 10,000-15,000 people worldwide, 95% of whom will develop numerous polyps in the bowel which eventually develop into colon cancer, usually before the age of 40. The gene is mutated in sporadic forms of colon cancer as well.
The researchers randomly assigned seven-week-old male mice to either voluntary wheel running or to no exercise for 10 weeks. For the first three weeks both groups had the same amount of food and water, but after that the exercising mice were fed the amount that the non-exercising mice had eaten the week before so that their food consumption was unable to rise with their increased activity, thereby producing a negative energy balance.
By the end of the ten weeks, six of the 23 control mice had died due to the number of polyps that had grown and the resulting anaemia, while all the 24 exercising mice were still alive.
"The exercising mice ran an average of 3.8 km a day, and the further they ran the fewer polyps they had. Exercise significantly reduced total polyp number and polyp size, as well as prolonging survival," said Dr Colbert. "On average there were 16 polyps per mouse in the exercising mice compared to 22 polyps in the control mice – a decrease of 25%."
* "Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice" and "Negative energy balance induced by voluntary wheel running inhibits polyp development in APC Min Mice". Carcinogenesis journal, published online 13 May 2006.
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