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 photodynamic therapy (PDT) of tumors. Porphyrins such as chlorophyll, chlorophyllin (CHL) and hemin are known to inactivate various mutagens by forming complexes with them. Tetrakis(4-benzoic acid)porphyrin (TBAP) has been developed as a photosensitizer for PDT and its metal complex, MnTBAP has been shown to be efficacious in a variety of in vitro and in vivo oxidative stress models of human diseases. In the present study, we have found that TBAP and hemin exert concentration-related inhibition of his(+) reversion in Salmonella typhimurium TA100 induced by 7, 12-dimethylbenz[a]anthracene (DMBA), and significantly reduced both incidence and multiplicity of skin tumors when topically applied prior to treatment of 12-O-tetradecanoylphorbol-13-acetate in female ICR mice. Covalent DNA binding of DMBA in mouse skin was also significantly inhibited by topical application of TBAP or hemin as well as CHL. These results suggest the chemopreventive potential of compounds containing a porphyrin nucleus.
Chung
W Y
WY
Department of Oral Biology, Yonsei University College of Dentistry, 120-752, Seoul, South Korea.
Lee
J M
JM
Lee
W Y
WY
Surh
Y J
YJ
Park
K K
KK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000493:pharmacokinetics; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D018736:DNA Adducts / Q000032:analysis; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D010778:Photochemotherapy; D012486:Salmonella typhimurium / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D018736:DNA Adducts; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D015127:9,10-Dimethyl-1,2-benzanthracene; D006427:Hemin