Porphyrin compounds have been known to inhibit mutations induced by several chemical carcinogens. The chemopreventive activity of porphyrin compounds were monitored by using 6-sulfooxymethylbenzo[a]pyrene (SMBP), which is an ultimate metabolite of benzo[a]pyrene. The porphyrin compounds were quite effective in reducing both cytotoxicity and mutagenicity for SMBP at the concentration of 10㎛. Their protective effect against the mutagenicity of SMBP was in the following decreasing order: hemin, chlorophyllin, biliverdin, protoporphyrin, chlorophyll b and chlorophyll a. The inhibitory patterns of hemin for SMBP was also confirmed in S. typhimurium strains TA98 and 100. Mutation frequency caused by SMBP was diminished almost to control level at 5 nmol hemin concentration. The inhibitory effects of hemin against the assault of SMBP in V79 cells was found to related to the reduced cellular uptake of SMBP and further the remarkably lowered DNA adducts. Furthermore, hemin suppresed the hepatic cytosol and PAPS-mediated covalent binding of HMBP to DNA, possibly through inhibition of hydroxysteroid sulfotransferase, which is responsible for the formation of sulfuric acid ester from the parent alcohol. The complex formation of hemin with SMBP was confirmed by solvent extraction and the hydrolysis product identified by reverse-phase HPLC. Such a complex formation will lead to decreased cellular uptake of SMBP. The inhibition of enzyme and the inactivation of sulfur acid ester metabolite are possible chemopreventive mechanisms of porphyrin compound against SMBP.
암 예방제로서 포르피린계 물질의 활성을 S. typhimurium TA98와 V79세포에서 SMBP의 돌연변이와 세포독성에 대한 실험으로 확인하였는데, 헤민이 가장 효과가 좋았고 클로로필린이 그 다음의 활성으로 가졌다. 헤민은 세포내로의 SMBP의 축적을 억제하고, DNA와의 결합도 줄였다. 그리고 젤상에서 pUC19 plasmid의 변화된 이동 상태를 정상으로 유지하였다. 그러나 헤민은 HMBP의 activation에 관여하는 hydroxysteroid sulfotransferase의 활성에는 미치는 영향이 적었고, 반면 DHEA는 특이적 억제효과를 나타내었다. 중요한 억제기전으로서 헤민과 SMBP와의 결합은 용매추출과 역상 HPLC로 확인하였다.
