Epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene via a hydroperoxide-dependent mechanism catalyzed by lipoxygenases

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Abstract
The lipoxygenase catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[α]pyrene (BP-7,8-diol) was examined. Epoxidation of the BP-7,8-diol was catalyzed by 5- and 15-lipoxygenase in the presence of either arachidonic acid, γ-linolenic add, or 15-hydroperoxyeicosatetraenoic acid (15-HPETE). The anti-9,10-epoxy-7,8-dihydroxy-7,8-dihydro benzo[α]pyrene isomer was formed in greater quantities than the syn isomer, indicative of peroxyl radical mediated epoxidation. Epoxidation was dependent on time, enzyme and fatty acid concentration. There was no difference in the time course of epoxidation with either arachidonic acid or 15-HPETE, although the initial rate of oxygen consumption was ∼55-fold greater with arachidonic acid. The lipoxygenase inhibior and anit-oxidant nordihydroguaiaretic acid inhibitor and anti-oxidant nordihydroguaiaretic acid inhinited epoxidation in a dose-dependent manner inincubations initiated with either arachidonic acid or 15-HPETE. The anti-oxidant butylated hydroxyanisole also inhibited the epoxidation. Incubations conducted under anaerobic conditions with 15-lipoxygenase and either arachidonic acid or 15-HPETE significantly decreased qpoxidation. This suggests that the oxygen inserted into BP-7-8-diol is derived from the atmosphere. The epoxidixing peroxyl radicals could not be detected by using the ESR spin trapping technique in incubations of 15-lipoxygenase with 15-HPETE. This radical. formed by reduction and rearrangement of the hydroperoxide, may trap oxygen toe form a peroxyl radical We propose that the epoxidizing species is a peroxyl radical derived from 15-HPETE rather than from arachidonic acid. This proposal is based on the similar amounts of epoxidation, but dissimilar amount of oxygen consumed with both fatty acids. Since lipoxygenases are widely distributed in vivo, especially in areas where tumors arise such as the pulmonary epithelium, peroxyl radical formation by these enxymes may have an important role in chemical carcinogenesis.

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