Constitutive expression of 8-lipoxygenase in papillomas and clastogenic effects of lipoxygenase-derived arachidonic acid metabolites in keratinocytes
✍ Scribed by Friederike Bürger; Peter Krieg; Andreas Kinzig; Bärbel Schurich; Friedrich Marks; Gerhard Fürstenberger
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 153 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
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.