Aryl hydrocarbon hydroxylase, epoxide hydrolase, and benzo[a]-pyrene metabolism in human epidermis: comparative studies in normal subjects and patients with psoriasis.
Prior studies have shown that human skin possesses a cytochrome P-450-dependent microsomal enzyme that is capable of metabolizing drugs and polycyclic aromatic hydrocarbon (PAH) carcinogens. This study characterized benzo[a]pyrene (BP) metabolism in human epidermis of normal and psoriatic individuals. The basal level of the cytochrome P-450-dependent microsomal enzyme aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH) were measured in freshly keratomed epidermis from 12 normal individuals and from uninvolved skin sites of 12 patients with psoriasis. The induction response of AHH following the in vitro addition of the PAH benz[a]anthracene (BA) was also assessed. The basal activity (mean +/- SE) of AHH in normal epidermis was 62.1 +/- 5.6 units (fmol 3-hydroxybenzo[a]pyrene, 3-OH-BP/min/mg protein) whereas the activity in uninvolved skin of psoriatic individuals was 62.9 +/- 5.1 units (NS), Epoxide hydrolase activity was 25.1 +/- 1.1 (pmol BP 4,5-diol/min/mg protein) unites in normal epidermis and 24.8 +/- 2.1 units in epidermis from patients with psoriasis (NS). Following addition of BA (100 microM), in vitro, AHH activity in normal epidermis increased by a mean value of 165% whereas activity in nonlesional epidermis of psoriatic individuals increased 320%. Kinetic studies in normal epidermis revealed that AHH reaction was linear up to 60 min and to 50 micrograms protein, had a pH optimum of 7.4, and the Km for BP was 0.62 microM. High-performance liquid chromatography (HPLC) confirmed that the pattern of metabolism of BP was quite similar in epidermal microsomes prepared from normal and psoriatic individuals, insofar as the formation of diols, phenols, and quinones was concerned. These studies indicate that human epidermis is capable of metabolizing BP and that there is no significant difference between normal individuals and patients with psoriasis insofar as basal AHH activity or total BP metabolism is concerned. Furthermore, the epidermal enzyme system in patients with psoriasis has a greater responsiveness to environmental PAH than does that of normal individuals.
D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis / Q000378:metabolism*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004817:Epidermis / Q000032:analysis / Q000201:enzymology*; D004851:Epoxide Hydrolases / Q000032:analysis / Q000378:metabolism*; D005470:Fluorometry; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D011565:Psoriasis / Q000201:enzymology*
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases