Microsomal Metabolism of 7-Nitrodibenz[a,h]anthracene: Effect of the Nitro Substituent on Regioselective Oxidative Metabolism

Abstract

7-Nitrodibenz[a,h]anthracene (7-nitro-DB[a,h]A) has been found to be less hepatocarcinogenic than its parent compound, dibenz[a,h]anthracene (DB[a,h]A). To examine the effect of the nitro functional group on metabolism, metabolism of 7-nitro-DB[a,h]A by rat liver microsomes was studied. The metabolites were purified by reversed-phase high pressure liquid chromatography and characterized by analysis of their UV-visible, mass and NMR spectral data. Four metabolites were identified, 7-nitro-DB[a,h]A trans-1,2-dihydrodiol, 7-nitro-DB[a,h]A trans-3,4-dihydrodiol, 2-hydroxy-7-nitro-DB[a,h]A, and 4-hydroxy-7-nitro-DB[a,h]A. The uniqueness of these metabolites is that they are all formed from metabolism at the 1,2,3,4-benzo ring of the 7-nitro-DB[a,h]A molecule. No metabolites derived from the other regions of 7-nitro-DB[a,h]A are found. Comparison of the metabolism results of 7-nitro-DB[a,h]A and DB[a,h]A indicates that the nitro substituent significantly affects the regioselectivity of the metabolism.

Key Words:

• 7-Nitrodibenz[a,h]anthracene (7-nitro-DB[a,h]A)
• 7-nitro-DB[a,h]A trans-1,2-dihydrodiol
• 7-nitro-DB[a,h]A trans-3,4-dihydrodiol
• 2-hydroxy-7-nitro-DB[a,h]A
• 4-hydroxy-7-nitro-DB[a,h]A
• microsomal metabolism.