Lung tumors in strain A mice: application for studies in cancer chemoprevention

Strain A mice develop a high incidence of spontaneous lung tumors during their lifetime. These tumors may be found in some animals as early as 3 to 4 weeks of age, increasing to nearly 100% by 24 months of age. The strain A mouse is also highly susceptible to the induction of lung tumors by several classes of chemical carcinogens and has been used extensively as a mouse lung tumor bioassay for assessing the carcinogenic activity of a variety of chemicals. In addition to its use in carcinogen detection, the strain A mouse lung tumor model has been employed extensively for the identification of inhibitors of chemical carcinogenesis. A number of chemopreventive agents including beta-naphthoflavone, butylated hydroxyanisole, ellagic acid, phenethyl isothiocyanate, phenylpropyl isothiocyanate, phenylbutyl isothiocyanate, phenylhexyl isothiocyanate, indole-3-carbinol, etc., have been shown to inhibit chemically induced lung tumors in strain A mice. In most instances, inhibition of lung tumorigenesis has been correlated with effects of the chemopreventive agent on the metabolic activation and/or detoxification of carcinogens. To date, no chemopreventive agent has been shown to inhibit lung tumorigenesis in strain A mice when administered after the carcinogen, i.e., during the promotion/progression stages of tumor development. Efforts should be made to develop a standardized protocol in strain A mice for evaluating chemopreventive agents as inhibitors of both the initiation and progression stages of lung tumor development.