Premium
Constitutive expression of 8‐lipoxygenase in papillomas and clastogenic effects of lipoxygenase‐derived arachidonic acid metabolites in keratinocytes
Author(s) -
Bürger Friederike,
Krieg Peter,
Kinzig Andreas,
Schurich Bärbel,
Marks Friedrich,
Fürstenberger Gerhard
Publication year - 1999
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199902)24:2<108::aid-mc5>3.0.co;2-r
Subject(s) - arachidonic acid , lipoxygenase , biology , epidermis (zoology) , linoleic acid , biochemistry , enzyme , keratinocyte , dmba , tumor promotion , carcinogenesis , microbiology and biotechnology , in vitro , gene , fatty acid , anatomy
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.