Byard, JL; Koepke, UC; Abraham, R; Goldberg, L; Coulston, F
In a study of the hepatic effects of Mirex, Charles River CD-1 mice were fed 1-90 ppm Mirex in the diet for periods ranging from 5 days to 13 months, Swiss Webster, BALB/c and C57 mice were fed 15 ppm Mirex for 4 months, and Sprague Dawley rats received 5 and 30 ppm Mirex for 13 and 9 months respectively. At regular intervals, heavy mitochondrial, light mitochondrial, microsomal and soluble fractions were prepared from livers of 2-6 animals/group. Measurements of DNA, protein, respiration, oxidative phosphorylation, mixed function oxidase, glucose-6-phosphatase and diene conjugates were carried out. Mirex stimulated an increase in relative liver weight which was slight at 1 ppm and 230% of the control value at 30 ppm. The protein in each liver fraction increased in approximate proportion to the increase in relative liver weight. Mixed function oxidase activity and cytochrome P-450 were stimulated several-fold in all livers. The total DNA content of the liver was elevated 120-360%, and tended to increase as the level of Mirex and the duration of feeding increased. While the amount of DNA in the liver increased, the DNA concentration decreased, indicating that new protein resulted from stimulation of RNA and/or protein synthesis as well as DNA synthesis. Respiration in the light mitochondrial fraction was stimulated 2- to 3-fold by Mirex. In comparison with controls, the mitochondria in this fraction has a more intact inner membrane, as measured by permeability to NADH, and a tighter coupling of oxidative phosphorylation to respiration. Decreased glucose-6-phosphatase activity was not associated with lipid peroxidation since the concentration of diene conjugates was unchanged. No marked sex differences were observed in the biochemical parameters in Charles River CD-1 mice. Strain differences were not evident in male Swiss Webster, BALB/c, C57 or CD-1 mice fed 15 ppm Mirex for 2 and 4 months. At comparable doses and lengths of exposure, the biochemical parameters were much less changed in rats than in mice. (Supported by Research Grant 2P01-ES00226-07 from the National Institute of Environmental Health Sciences, NIH, and by National Institutes of Health Training Grant 2T01-ES00103-07.)