ABSTRACT
Perfluorinated fatty acids are metabolically stable analogues which exhibited equal or greater potency as peroxisome proliferators than CPIB in primary cultured hepatocytes. In this regard the rank order of potency for inductidn of LH and FACO activities was the same (PFOA>PFDA>PFBA=CPIB), and is a characteristic coinduction enzyme response that has previously reported for peroxisome proliferators in cultured hepatocytes (Lake et al., 1984; Kocarek and Feller, 1987; Sharma et al., 1988; Gibson et al., 1990). The same rank order of in vivo peroxisome proliferative activity has been reported in rats administered these perfluorinated fatty acids (Ikeda et al., 1985; Kozuka et al., 1991). Whereas Ikeda et al. (1985) reported that a single injection of PFOL to rats caused in vivo peroxisome proliferation using hepatic catalase as a biochemical marker, our studies showed that PFOL was unable to induce either LH or FACO activities. Thus, the results indicate that either the oxidation of PFOL occurs to a significant degree only in vivo, or PFOL acts through an indirect mechanism independent of the liver (e.g. hormone-mediated action). As reported previously (Intrasuksri and Feller, 1991), our studies demonstrate that the carboxylic acid group and carbon chain length are important structural determinants of perfluorinated fatty acid mediated peroxisome proliferation in cultured hepatocytes ( Figure 16.2).
