0000000000085527
AUTHOR
Charles A. Kirkby
Metabolic activation to a mutagen of 3-hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, a secondary metabolite of benzo[a]pyrene
3-Hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (3-OH-BP-7,8-diol) was isolated from arylsulfatase/beta-glucuronidase-treated bile of rats to which 3-hydroxybenzo[a]pyrene (3-OH-BP) has been administered. This triol was investigated for mutagenicity in Salmonella typhimurium (reversion to histidine prototrophy of strains TA 97, TA 98, TA 100 and TA 1537) and in V79 Chinese hamster cells (acquisition of resistance to 6-thioguanine). When no exogenous metabolizing system was added the triol was inactive, while 3-OH-BP showed weak mutagenic effects with all four bacterial strains. In the presence of NADPH-fortified postmitochondrial supernatant fraction (S9 mix) of liver homogenate fro…
Complex Metabolic Activation Pathways of Polycyclic Aromatic Hydrocarbons: 3-Hydroxy-trans-7,8-Dihydroxy-7,8-Dihydrobenzo[a]Pyrene as a Proximate Mutagen of 3-Hydroxybenzo[a]Pyrene
3-Hydroxybenzo[a]pyrene (3-OH-BP) is a major metabolite of benzo[a]pyrene (BP) in various systems. Metabolites of 3-OH-BP, formed by liver enzymes, bind to DNA1,2 and are mutagenic3,4. However, the active species have not yet been identified. Administration of 3-OH-BP to rats results in the excretion of sulfate and glucuronic acid conjugates of 3-hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (3-OH-BP-7,8-diol) (Fig. 1) as major metabolites in the bile5. The hydroxyl groups of this triol are structurally superimposable to those of 9-hydroxy-trans-1,2-dihydroxy-1,2-dihydrochrysene (9-hydroxychrysene-1,2-diol, Fig. 1), which is a metabolite of chrysene6,7 and a potent promutagen8,9. 9-…