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Cold mice may be skewing cancer tests

Temperature bias Tumours in lab mice grow faster than normal because of the cool temperatures the animals are kept at, and this could be giving misleading results in cancer drug tests, say US researchers.

They believe lab mice are probably spending too much energy keeping warm and not enough energy on their immune response against cancer.

"Cancer therapy testing in mice could be skewed by the fact that our control groups are not controlling tumour growth as well as they could be," says co-author Dr Elizabeth Repasky, a professor of immunology at the Roswell Park Cancer Institute in Buffalo, New York.

"I'm afraid that we're getting information that has been influenced by the fact that the animals are feeling cold."

Repasky says laboratories around the world are required to keep laboratory mice between 20 and 26°C - often at the cooler end of this.

This ensures lab workers are comfortable and do not have to change the mouse cages too often, and it is an advantage for researchers, because mice also tend to have bigger litters when it is cold.

But, says Repasky, healthy mice are known to prefer ambient temperatures of 30-31°C.

She says some studies from the field of obesity research, have suggested 'housing temperatures' could be a problem because the mice will feel cold and not respond in the way they normally would.

To test whether this was an issue in cancer research, Repasky and colleagues compared tumour formation, growth rate, and metastasis in mice that were cold stressed at 22-23 °C and those who were not cold stressed at 30-31°C.

They found five different kinds of tumours grew slower in mice housed at 30°C than in mice housed at 22°C, even though both groups of mice maintained normal body temperature.

"We were very surprised to see that the animals that were not cold stressed could control the growth of their tumour much better," says Repasky.

The researchers found that in such animals, killer T lymphocytes levels rose in tumours while immunosuppressive cells levels dropped, indicating a boost to the animal's immune response.

Repasky and colleagues confirmed that, given a choice, healthy mice preferred temperatures that were warmer than housing temperatures, and those with cancer felt the cold even more.

She says it is likely cold-stressed mice with cancer would be spending their energy keeping warm instead of mounting an immune response to the disease.

Implications for research

Repasky says the findings flag an issue for drug cancer testing that compare a control group of mice (not given the drug) with a treatment group (given the drug).

The cool housing temperatures may mean the control group are not fighting the cancer as well as an unstressed mouse would, which could make the drug appear more effective than it really is in the treatment group.

"This might explain why some drugs when they go into the clinic don't work as well as would have been predicted from the mouse models," says Repasky.

She says the low temperatures could also skew results in the opposite direction, by making the tumour more resistant to the mouse immune response.

"A drug that fails to show an effect might in fact work in an animal that is not stressed," says Repasky.

The researchers now intend to go back and test the effect of housing temperature on drugs that have failed during clinical trials, or that have not gone forward to clinical trials due to negative findings in laboratory mice.

Immunology research

Quite apart from the impact on cancer drug tests, housing temperature could also affect basic immunology research, says Repasky.

"Basic immunology information that is coming from mice may be skewed by the fact that these animals are cold," she says.

Repasky says it would not be practical to increase the housing temperature of mice but there are other things that could be done to remedy the situation.

"We could give them more bedding to make warmer nests. Another way to do it is to add more mice to the cage because mice in nature like to huddle in big groups and that keeps them warmer," she says.

The findings appear in this week's Proceedings of the National Academies of Science.