ABSTRACT
Species differences in sensitivity A pronounced species difference in the chemical induction of hepatocellular peroxisome proliferation has been reported by numerous researchers (reviews cited above; Rodericks and Turnbull, 1987; Short et al., 1987; Lake et al., 1989a; Watanabe et al., 1989). Table 30.1 summarizes the peroxisome morphological and enzymological data available for several known peroxisome proliferative agents in a variety of mammalian species. While some variability in the relative rodent versus higher mammalian species responses to these compounds is evident, it is clear from these data that higher mammalian species are considerably less sensitive or completely refractory to known peroxisome proliferative agents at maximal tolerated and/or therapeutic dosages. Thus, compounds such as gemfibrozil, fenofibrate, LY17883, nafenopin and clobuzarit, which cause as much as 10-to 35-fold increases in the number of hepatocellular peroxisomes and/or induction of peroxisomal enzymes in rodents, cause only slight increases or no change in peroxisomal number and enzyme activity in dogs and non-human primates at much higher dosages.
