TOTAL-BODY CLEARANCE OF CIRCULATING BENZO(A)PYRENE IN CONSCIOUS RATS - EFFECT OF PRETREATMENT WITH 3-METHYLCHOLANTHRENE AND THE ROLE OF LIVER AND LUNG

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (3) , 661-667
Abstract
The metabolic clearance of benzo(a)pyrene [B(a)P] was studied in conscious control and 3-methylcholanthrene (3-MC)-pretreated rats. The roles of liver and lung in total body B(a)P clearance were estimated in vivo in 3-MC-treated rats. During a 5 h period, blood B(a)P concentration decreased rapidly in a biphasic manner. 3-MC pretreatment did not significantly affect the rate constants of B(a)P elimination, but the apparent volume of distribution increased, resulting in an increase in total body B(a)P clearance from 15 .+-. 1 to 48 .+-. 6 ml/min. Five hours after injection, B(a)P concentrations in most organs were lower in 3-MC-pretreated rats; lung B(a)P concentration was greater. In the 3-MC-pretreated rats, 1st-pass extraction of B(a)P by lung and liver was determined from comparison of areas under arterial blood B(a)P concentration vs. time curves after intraarterial, i.v. and intraheptic portal venous administration. Liver had a 1st-pass extraction of 20%, that by lung was 33%. Organ B(a)P concentrations were correlated with the route of B(a)P administration. 3-MC pretreatment increased the apparent volume of B(a)P distribution in vivo, liver and lung of 3-MC-pretreated rats were about equal in their ability to extract circulating B(a)P in vivo and 3-MC pretreatment enhanced total body B(a)P clearance by increasing extrahepatic B(a)P elimination.