ULTRASTRUCTURAL, PROTEIN, AND LIPID CHANGES IN LIVER ASSOCIATED WITH CHLORDECONE TREATMENT OF MICE

Pretreatment of mice with chlordecone (CD) reduced hepatic accumulatio n of a subsequent dose of [C-14]CD without significantly changing [C-1 4]CD biotransformation. To determine if CD-induced changes in hepatic [C-14]CD accumulation were coincident with altered cell composition, w e examined the effects of CD on hepatic protein and lipid content, on fatty acid profiles of liver and kidney, and on the ultrastructure of hepatocytes. SDS-polyacrylamide gel electrophoresis detected an appare nt CD dose-related increase in a microsomal protein with a molecular w eight of about 23 kDa. Total liver or kidney lipid contents were not a ltered by CD but relative amounts of several hepatic fatty acids were changed. CD caused marked hepatic mitochondrial swelling, increased am ounts of endoplasmic reticulum, apparently increased numbers of peroxi some-like structures, and decreased numbers of lipid droplets in cytop lasm of hepatocytes. Numbers of lipid droplets were not decreased in p erisinusoidal fat storage cells. In addition, the numbers of cytoplasm ic lipoprotein vesicles were apparently increased in some hepatocytes. Overall these changes indicated an increased hepatocyte secretory act ivity and suggested that CD changed hepatocellular lipid transport, st orage, and metabolism pathways. (C) 1996 Society of Toxicology.