Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis

Murine and human skin express an abundance of lipoxygenase isoforms whose f unctions are not understood. Substantial data have implicated a role for th e 'platelet-type' 12-lipoxygenase (P-12LO) metabolite, 12(S)-hydroxy-eicosa tetraenoic acid (12-HETE), in a variety of tumor functions. Using P-12LO de ficient mice, we sought to examine the role of the P-12LO pathway in tumor initiation and progression. Two distinct genetic strains of P-12LO deficien t and wild-type mice, B6/129 Sv and SENCAR, were evaluated in two-stage car cinogenesis experiments. Carcinoma incidence was significantly reduced in t he P-12LO deficient mice of the B6/129 Sv background but not the SENCAR-bac kcrossed mice. In contrast, papilloma incidence was reduced on the SENCAR b ackground but not in the B6/129 Sv strain mice. A separate experiment emplo ying a complete carcinogenesis protocol failed to find any difference in pa pilloma or carcinoma incidence. Overall, these data suggest that the P-12LO pathway may contribute to tumor incidence and progression in two-stage, bu t not complete, carcinogenesis, depending on the genetic background. (C) 20 01 Elsevier Science ireland Ltd. All rights reserved.