11,12-Epoxy-9,10,11,12-tetrahydro-5,9,10-trihydroxybenzo[b]fluoranthene: Its Role in the Metabolic Activation of B[b]F in Mouse Skin

Abstract

The skin tumor-initiating activity of benzo[b]fluoranthene (B[b]F), 9,10-dihydro-5,9,10- and 6,9,10-trihydroxybenzo[b]fluoranthenes (5- and 6-OH-B[b]F-9,10-diols) is reported in the present study. DNA adduct formation with B[b]F and the synthetic reference standards, 9,10-dihydro-9,10-dihydroxybenzo[b]fluoran-thene (B[b]F-9,10-diol), 5-OH-B[b]F-9,10-diol, 6-OH-B[b]F-9,10-diol, and their respective dihydrpdiol epoxides was investigated using ³²P-postlabeling analysis with multidimensional TLC and reverse-phase HPLC. These comparative studies indicate that the genotoxicity posed by B[b]F in mouse skin is primarily due to adduct formation from 11,12-epoxy-9,10,11,12-tetrahydro-5,9,10-trihydroxybenzo-[b]fluoranthene (5-OH-B[b]F-9,10-DE) and a guanylic moiety of DNA.

Key Words:

• Benzo[b]fluoranthene
• 9,10-dihydro-5,9,10-trihydroxybenzo[b]fluoranthene
• 11,12-epoxy-9,10,11,12-tetrahydro-5,9,10-trihydroxybenzo[b]fluoranthene
• DNA adduct
• metabolic activation
• ³²P-postlabeling