Perfluorinated fatty acids (PFCAs), in which all aliphatic hydrogen atoms are substituted by fluorine, are primarily used as a reactive intermediate, while their salts are used as processing aids in the production of fluoropolymers and fluoroelastomers and in other surfactant uses. PFCAs have very low volatility and vapor pressure and are not hydrolyzed, photolyzed, or biodegraded under environmental conditions. Several investigators have studied the effects of PFCAs on biological systems. The administration of perfluorooctanoic acid (C8), a PFCA with 8 carbon atoms, to male rats is known to cause marked hepatomegaly and peroxisome proliferation.1) Moreover, various enzymes involved in lipid metabolism and drug metabolism were reported to be induced in the liver by the administration of C8 to male rats. [2][3][4][5][6] In addition to the above-mentioned effects, C8 accumulates triglyceride (TG) in the liver of male rats. 4) Perfluorodecanoic acid (C10), a PFCA with a 10 carbon chain length, has also been reported to cause considerable lipid accumulation in the liver of male rats, 7) and the potency of C10 in TG accumulation appears to be much greater than that of C8. 4,7) These results raise the question of whether the induction of hepatic TG accumulation is specific to PFCAs with longer carbon chain lengths. There is another major difference in the induction of enzymes such as peroxisomal b-oxidation between C8 and C10. The treatment of male rats with C8 induced marked peroxisomal b-oxidation in the liver, whereas little induction was observed in female rats. [8][9][10] Nevertheless, the administration of C10 caused marked induction of peroxisomal b-oxidation in the liver of both male and female rats.10) To the best of our knowledge, no information is available about sexrelated difference in the effects of C10 on hepatic lipid accumulation.In this study, we aimed to investigate the relationship between the effects of PFCAs on hepatic TG levels and the carbon chain length of PFCAs. Moreover, we compared the induction of TG accumulation with the induction of peroxisomal b-oxidation in the liver. and Triton X-100 was from Nakalai Tesque (Kyoto, Japan). 3-Bromoacetyl-7-methoxycoumarin was prepared as previously described.
MATERIALS AND METHODS
Materials11) All other chemicals used were of analytical grade.Animals Male and female Wistar rats aged 5 weeks were purchased from SLC (Hamamatsu, Japan). After acclimatization for 1 week, rats received intraperitoneal injections of C7, C8, C9, or C10 once a day for 5 d. PFCAs were dissolved in propyleneglycol : water (1 : 1, v/v) after neutralization with equimolar NaOH. All rats received a dosing volume of 1 ml/kg body weight.Some male rats (24-26 d old) were castrated. Four days after castration, the rats were administered testosterone propionate dissolved in corn oil at a dose of 10 mg/kg body weight or vehicle alone every 2 d for 3 weeks. These rats The potency to accumulate triglyceride (TG) was compared between perfluorinated fatty acids (PFCAs) with different carbon...