Protective effects of hemin and tetrakis(4-benzoic acid)porphyrin on bacterial mutagenesis and mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene

Porphyrins which are widespread in nature can interfere with the actions of certain carcinogens and mutagens, and have also been used clinically in ph otodynamic therapy (PDT) of tumors. Porphyrins such as chlorophyll, chlorop hyllin (CHL) and hemin are known to inactivate various mutagens by forming complexes with them. Tetrakis(4-benzoic acid)porphyrin (TBAP) has been deve loped as a photosensitizer for PDT and its metal complex, MnTBAP has been s hown to be efficacious in a variety of in vitro and in vivo oxidative stres s models of human diseases. In the present study, we have found that TBAP a nd hemin exert concentration-related inhibition of his(+) reversion in Salm onella typhimurium TA100 induced by 7,12-dimethylbenz[a]anthracene (DMBA), and significantly reduced both incidence and multiplicity of skin tumors wh en topically applied prior to treatment of 12-O-tetradecanoylphorbol-13-ace tate in female ICR mice. Covalent DNA binding of DMBA in mouse skin was als o significantly inhibited by topical application of TBAP or hemin as well a s CHL. These results suggest the chemopreventive potential of compounds con taining a porphyrin nucleus. (C) 2000 Elsevier Science B.V. All rights rese rved.