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Int. J. Mol. Sci. 2002, 3(9), 1008-1018; doi:10.3390/i3091008
Article

In Vitro Metabolism of Dibenzo[a,l]pyrene, 2-Chlorodibenzo [a,l]pyrene and 10-Chlorodibenzo[a,l]pyrene - Effects of Chloro Substitution

1,* , 1, 2, 2, 2, 3 and 4,*
1 Hungkuang Institute of Technology, Sha-Lu, Taichung, Taiwan 2 National Center for Toxicological Research, Jefferson, AR 72079, USA 3 Department of Biology, Jackson State University, Jackson, MS 39217, USA 4 Department of Chemistry, Jackson State University, Jackson, MS 39217, USA
* Authors to whom correspondence should be addressed.
Received: 7 June 2002 / Accepted: 15 August 2002 / Published: 30 September 2002
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Abstract

Stereoselective metabolism of dibenzo[a,l]pyrene (DB[a,l]P), 2-chlorodibenzo[a,l]pyrene (2-Cl-DB[a,l]P) and 10-chlorodibenzo[a,l]pyrene (10-Cl-DB[a,l]P) by rat liver microsomes was studied and effects of the chloro substituent on the metabolism were determined. All three compounds produced trans-8,9-dihydrodiol, trans-11,12-dihydrodiol, and the 7-hydroxyl derivative as major metabolic products and several other phenolic derivatives as minor metabolites. The trans-8,9- and 11,12-dihydrodiols of DB[a,l]P and 2-Cl-DB[a,l]P preferentially adopted a quasidiequatorial conformation, whereas 10-Cl-DB[a,l]P trans-8,9- and 11,12-dihydrodiols preferentially adopted a quasidiaxial conformation. The yields of the trans-11,12-dihydrodiol metabolites are: DB[a,l]P trans-11,12-dihydrodiol > 2-Cl-DB[a,l]P trans-11,12-dihydrodiol >> 10-Cl-DB[a,l]P trans-11,12-dihydrodiol. Circular dichroism (CD) spectral analysis indicates that the trans-8,9-dihydrodiol and trans-11,12-dihydrodiol metabolites from DB[a,l]P, 2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P are optically active. Furthermore, the major enantiomeric DB[a,l]P trans-11,12-dihydrodiol and 2-Cl-DB[a,l]P trans-11,12-dihydrodiol had R,R absolute configuration. Based on the fact that DB[a,l]P trans-11,12-dihydrodiol is the proximate tumorigenic metabolite of DB[a,l]P, our results suggest that DB[a,l]P exhibits the highest tumorigenic potency followed by 2-Cl-DB[a,l]P, and 10-Cl-DB[a,l]P exhibits the lowest tumorigenicity.
Keywords: Microsomal metabolism; dibenzo[a; l]pyrene; 2-chlorodibenzo[a; l] pyrene; 10- chlorodibenzo[a; l]pyrene Microsomal metabolism; dibenzo[a; l]pyrene; 2-chlorodibenzo[a; l] pyrene; 10- chlorodibenzo[a; l]pyrene
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Wu, Y.-S.; Fang, G.-C.; Moody, J.; Von Tungeln, L.S.; Fu, P.P.; Hwang, H.-M.; Yu, H. In Vitro Metabolism of Dibenzo[a,l]pyrene, 2-Chlorodibenzo [a,l]pyrene and 10-Chlorodibenzo[a,l]pyrene - Effects of Chloro Substitution. Int. J. Mol. Sci. 2002, 3, 1008-1018.

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