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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,*
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

Wu Y-S, Fang G-C, Moody J, Von Tungeln LS, Fu PP, 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. International Journal of Molecular Sciences. 2002; 3(9):1008-1018.

Chicago/Turabian Style

Wu, Yuh-Shen; Fang, Guor-Cheng; Moody, Joanna; Von Tungeln, Linda S.; Fu, Peter P.; Hwang, Huey-Min; Yu, Hongtao. 2002. "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. 3, no. 9: 1008-1018.



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