© 1991 Oxford University Press
research-article |
Suppression of benzo[a]pyrene metabolism by accumulation of triacylglycerols in rat hepoatacytes: effect of high-fat and food-restricted diets
Laboratory for Cellular and Biochemical Toxicology, Rutgers University Piscataway, NJ 08854, USA
1Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina School of Medicine Chapel Hill, NC 27599, USA
Diet has been implicated as a major determinant of chemical carcinogenesis. Accordingly, rates of benzo[a]pyrene (B[a]P) metabolism were compared in hepatocytes isolated from rats maintained on control, high-fat or food-restricted AIN-76A diets. Rats maintained on the food-restricted diet were given 65% of food consumed by the control group fed ad libitum. The high-fat diet group had free access to a modified AIN-76A diet in which the amount of corn oil was increased 4-fold at the expense of digestible carbohydrates. The triacylglycerol content in hepatocytes varied in direct proportion to dietary fat and calories and was 66 ± 5, 105 ± 7 and 192 ± 16 nmol/mg dry wt in cells isolated from rats fed food-restricted, control and high-fat diets respectively. In contrast, the rate of B[a]P metabolism was highest in hepatocytes from rats maintained on the food-restricted diet and lowest in cells from animals given the high-fat diet (i.e. food-restricted > control > high-fat). Thus, an inverse correlation existed between the rate of B[a]P metabolism and the content of triacylglycerols in hepatocytes. At a cell density of {small tilde}2 mg dry wt/ml, rates of B[a]P (40 µM) metabolism were 1324 ± 186, 1150 ± 198 and 829 ± 76 pmol/mg dry wt/h, respectively, in hepatocytes isolated from rats fed food-restricted, control and high-fat diets. When cells were incubated with a lower concentration of B[a]P (10 µM), the rate of B[a]P metabolism was > 2-fold higher in hepatocytes from rats fed the food-restricted diet compared to the rate measured in cells from the high-fat group. Glucuronidation of B[a]P metabolites in hepatocytes from rats fed high-fat diet was also {small tilde}30% lower than rates determined for control and food-restricted groups. These diet-induced alterations in rates of B[a]P metabolism occurred in the absence of changes in specific activity of arylhydrocarbon hydroxylase or UDP-glucuronosyltransferase in liver microsomes. Further, the rate of 7-ethoxycoumarin metabolism, a more hydrophilic substrate, was not affected by diet and B[a]P but not 7-ethoxycoumarin accumulated in hepatic lipid droplets. Thus, diet-induced changes in intracellular triacylglycerol, particularly in lipid droplets, may alter access of B[a]P to binding sites on arylhydrocarbon hydroxylase and thereby modulate B[a]P metabolism in intact hepatocytes.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Ramesh, S. A. Walker, D. B. Hood, M. D. Guillen, K. Schneider, and E. H. Weyand Bioavailability and Risk Assessment of Orally Ingested Polycyclic Aromatic Hydrocarbons International Journal of Toxicology, September 1, 2004; 23(5): 301 - 333. [Abstract] [Full Text] [PDF]
|
|