Antimutagenicity of porphyrin derivatives and stabilizing effect of albumin against 6-Sulfooxymethylbenzo[a]pyrene = 6-설폭시메칠벤조피렌에 대한 포르피린 유도체의 항 돌연변이성과 알부민의 안정화 효과에 관한 연구

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The 6-hydroxymethylbenzo[a]pyrene (HMBP) is converted to electrophilically reactive HMBP 6-sulfate (SMBP) in the presence of 3``-phosphoadenosine-5`` -phosphosulfate (PAPS) by sulfotransferase in rat liver. Both HMBP and SMBP were equally strong mutagenic in S. typhimurium strains TA98 and TA100. SMBP also appeared to be mutagenic and cytotoxic in Chinese hamster V79 cells where mutation rate at theNa/K-ATPase and hypoxanthine:guanine phophoribosyltransferase (HGPRT) loci were measured by the resistance to ouabain and 6-thioguanine (6-TG), respectively. Mutation frequencies induced by HMBP and its sulfate derivative at the HGPRT locus were higher than at the Na/K-ATPase locus. The electrophilic sulfuric ester form produced adducts in macromolecules such as DNA and protein in V79 cells, suggesting that mutagenic activity of SMBP derives from the formation of macromolecular adducts, especially DNA adducts. The peak maxima of the fluorescence emission spectra of B[a]P-chromophore was shifted to the longer wavelength regions as DNA was incubated with SMBP, indicating that the highly covalent binding of SMBP with DNA bases may be assumed to be attributable to the intercalation of strongly anionic molecules into the DNA base pairs. This assumption was supported by the results from equilibrium dialysis. Noncovalent interaction between B[a]P moiety and DNA may provide a favorable condition for adduct formation. It was also found that the binding of SMBP to calf thymus DNA was much more efficient than the binding of HMBP in metabolic activation. SMBP binding to DNA was also confirmed by the analysis of electrophoregram of SMBP-modified plasmid. Chlorophyllin (CHL), a water soluble salt of chlorophyll a, has been known to inhibit mutations induced by several chemical carcinogens. The chemopreventive activity of CHL was measured against HMBP and SMBP in microbial and mammalian cell systems. CHL was quite effective in reducing both cytotoxicity and mutagenicity of SMBP in...
Advisors
Chung, An-Sik정안식
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
1996
Identifier
108910/325007 / 000925364
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생물과학과, 1996.8, [ xiii, 141 p. ]

Keywords

Stabilizing Effect; Albumin; Porphyrin derivatives; Antimutagenicity; SMBP; 6-설폭시메칠벤조피렌; 안정화효과; 알부민; 포르피린 유도체; 항돌연변이

URI
http://hdl.handle.net/10203/27394
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=108910&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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