Total body clearance of circulating benzo(a)pyrene in conscious rats: effect of pretreatment with 3-methylcholanthrene and the role of liver and lung.

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-hr 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; however, lung B(a)P concentration was greater. In the 3-MC-pretreated rats, first-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 i.a., i.v. and intrahepatic portal venous administration. Liver had a first-pass extraction of 20% whereas that by lung was 33%. Organ B(a)P concentrations were correlated with the route of B(a)P administration. The results of this study suggest that 1) 3-MC pretreatment increases the apparent volume of B(a)P distribution in vivo, 2) liver and lung of 3-MC-pretreated rats are about equal in their ability to extract circulating B(a)P in vivo and 3) 3-MC pretreatment enhances total body B(a)P clearance by increasing extrahepatic B(a)P elimination.