Weaknesses and Pitfalls of Using Mice and Rats in Cancer Chemoprevention Studies

Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals with a much longer lifespan should be used to bridge the lifespan gap between the rodents and humans. There are many transgenic mouse models of carcinogenesis available, in which DNA promoters are used to activate transgenes. One promoter may activate the transgene in multiple cell types while different promoters are activated at different ages of the mice. These spatial and temporal aspects of transgenes are often neglected and may be pitfalls or weaknesses in chemoprevention studies. The variation in the copy number of the transgene may widen data variation and requires use of more animals. Models of chemically-induced carcinogenesis do not have these transgene-related defects, but chemical carcinogens usually damage metabolic organs or tissues, thus affecting the metabolism of the chemopreventive agents. Moreover, many genetically edited and some chemically-induced carcinogenesis models produce tumors that exhibit cancerous histology but are not cancers because the tumor cells are still mortal, inducer-dependent, and unable to metastasize, and thus should be used with caution in chemoprevention studies. Lastly, since mice prefer an ambient temperature of 30-32°C, it should be debated whether future mouse studies should be performed at this temperature, but not at 21-23°C that cold-stresses the animals.