Augmentation of 12-O-tetradecanoyl 13-phorbol acetate-mediated tumor promoting response by the porphyrin photosensitization of 7,12-dimethyl benz[alpha]anthracene-initiated murine skin: role of in situ generated reactive oxygen species

Recently, we have shown that sustained ROS generation by prolonged porphyri n-mediated photosensitization in murine skin acts as a stage I and weak com plete tumor promoter. Further to this, in the present study, we show that p orphyrin photosensitization of DMBA-initiated murine skin results in the au gmentation of TPA-mediated tumor promoting response. The photosensitization increased tumor yield to 15 tumors per mouse as compared to 7.5 tumors per mouse in the group treated with TPA alone. Further, 100% tumor incidence i n the TPA-treated photosensitized group occurred at week 11 whereas it occu rred at week 19 in the TPA alone treated group. Porphyrin photosensitizatio n slightly decreased the latency period of TPA-mediated tumor formation by 1 week. The TPA-mediated ODC induction (1300% of saline-treated control) ha s been augmented in the photosensitized group (1950%). However, the amount of [H-3]thymidine incorporation was not significantly different in the phot osensitized TPA-treated and TPA alone-treated groups. Similarly, TPA treatm ent in photosensitized animals augmented the depletion of cutaneous glutath ione and enhancement of Lipid peroxidation. These changes were attenuated i n butylated hydroxytoluene-pretreated animals. Our results suggest that cut aneous porphyrin photosensitization augments TPA-mediated tumor promotion i n murine skin. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.