Constitutive expression of 8-lipoxygenase in papillomas and clastogenic effects of lipoxygenase-derived arachidonic acid metabolites in keratinocytes

• Verfasst von: Bürger, Friederike [VerfasserIn]
• Verfasst von: Krieg, Peter [VerfasserIn]
• Verfasst von: Schurich, Bärbel [VerfasserIn]
• Verfasst von: Marks, Friedrich [VerfasserIn]
• Verfasst von: Fürstenberger, Gerhard [VerfasserIn]
• Titel: Constitutive expression of 8-lipoxygenase in papillomas and clastogenic effects of lipoxygenase-derived arachidonic acid metabolites in keratinocytes
• Verf.angabe: Friederike Bürger, Peter Krieg, Andreas Kinzig, Bärbel Schurich, Friedrich Marks, and Gerhard Fürstenberger
• E-Jahr: 1999
• Jahr: 12 March 1999
• Umfang: 10 S.
• Teil: volume:24
• Teil: year:1999
• Teil: number:2
• Teil: pages:108-117
• Teil: extent:10
• Fussnoten: Gesehen am 21.04.2021
• Titel Quelle: Enthalten in: Molecular carcinogenesis
• Ort Quelle: New York, NY : Wiley Interscience, 1988
• Jahr Quelle: 1999
• Band/Heft Quelle: 24(1999), 2, Seite 108-117
• ISSN Quelle: 1098-2744
• DOI: doi:10.1002/(SICI)1098-2744(199902)24:2<108::AID-MC5>3.0.CO;2-R
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 8-lipoxygenase
• Sach-SW: clastogenic effects
• Sach-SW: keratinocytes
• Sach-SW: multistage mouse skin carcinogenesis
• K10plus-PPN: 1755608527

Abstract

The expression pattern, enzymatic activity, and products of 8-lipoxygenase (LOX) were analyzed in normal and neoplastic skin of NMRI mice. While barely detectable in normal epidermis, 8-LOX was transiently induced by 12-O-tetradecanoylphorbol-13-acetate and constitutively expressed in papillomas but not carcinomas obtained by the initiation-promotion protocol of mouse skin carcinogenesis. The product profile and chirality of both the native and the recombinant protein produced the S enantiomers of 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE) and 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE) as the main arachidonic acid- and linoleic acid-derived metabolites. As compared with normal epidermis, papillomas exhibited 25- and 4-fold elevated levels of 8-HETE and 9-HODE, respectively. However, the varying S to R ratios of 8-HETE and the predominance of 9(R)-HODE indicated that in addition to 8(S)-LOX, other enzymes yet to be defined may be involved in 8-HETE and 9-HODE production. The massive accumulation of both 8-HETE and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) point to a critical role of these LOX pathways in epidermal tumor development, in particular in the papilloma stage. Here we showed that 8- and 12-hydroperoxyeicosatetraenoic acids and 8- and 12-HETE induce chromosomal alterations in cycling primary basal keratinocytes. Mol. Carcinog. 24:108-117, 1999. © 1999 Wiley-Liss, Inc.