- Full (HTML) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Kevin M. Kleinow, ¹ Margaret O. James, ² Zeen Tong, ² and Changaram S. Venugopalan ¹

¹ Department of Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803 USA
² Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610 USA

Abstract

In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo( a ) pyrene (BaP) . Dietary organisms vary in their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers. This study examined the effect of dose and previous dietary exposure to the inducer ß-naphthoflavone (BNF) upon the intestinal metabolism of BaP and the systemic bioavailability of BaP-derived products in catfish. BaP was administered at 2 and 20 µM into in situ -isolated perfused intestines of control and BNF-pretreated catfish. The intestine formed an array of metabolites in all treatments including potentially hazardous metabolites such as BaP-7,8 and 9,10 dihydrodiols and 6-methyl-BaP. BNF treatment disproportionally increased the contribution of BaP-7,8 and 9,10 dihydrodiols relative to the contributions of other metabolites. A greater percentage of metabolites was evident as conjugates in 2 µM controls, whereas a greater percentage of unconjugated metabolites was evident for 20 µM controls and BNF treatments of both dosages. BNF pretreatment and the higher 20 µM BaP dosage resulted in greater bioavailability, with 2.6-5.5-fold and 3.0-6.3-fold increases in systemically available BaP products, respectively. Metabolites represented 10.2-23.1% of the increased bioavailability with BNF treatment, suggesting that mechanisms, in addition to induced metabolism, may be operative. These results indicate that intestinal bioavailability, level of biotransformation, and the metabolic profile of BaP-derived products entering the blood from the intestine may be altered by dose and dietary BNF pretreatment. Key words : activation, benzo( a ) pyrene, bioavailability, biotransformation, catfish, elimination, in situ preparation, intestine. Environ Health Perspect 106:155-166 (1998) . [Online 5 February 1998]

http://ehpnet1.niehs.nih.gov/docs/1998/106p155-166kleinow/ abstract.html

Address correspondence to K. Kleinow, Department of Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, South Stadium Drive, Louisiana State University, Baton Rouge, LA 70803 USA.

The authors acknowledge the technical assistance of Ernestine Holmes, Shashidar Mugadi, Judy Wiles, and Andrea Smith. B.H. Pollock, Department of Health Policy and Epidemiology, University of Florida, provided valuable statistical assistance. This work was supported by NIEHS grant ES 05781 (MOJ, KMK) . Portions of this work were presented at the Society of Toxicology Meeting, Dallas, TX, 1994.

Received 14 July 1997 ; accepted 5 November 1997.