| ABSTRACT: |
|
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. |