- 作者: 林仁混
- 作者服務機構: 台灣大學生化研究所
- 中文摘要: Most amides are stable compounds, but they are convertible to extremely reactive metabolites by microsomal enzymes. The amide drugs phenacetin and acetaminophen are converted to the toxic metabolite N-acetyl-p-benzoquinoneimine by a combination of several cytochrome P-450 systems. The well known hepatocarcinogen 2-acetylaminofluorene (AAF) is metabolically activated to a highly electrophilic reactant that interacts with DNA, RNA and proteins. There are other alternative pathways which may activate these amide compounds; nitrosation of these amides yield several directly acting mutagens, teratogens and carcinogens. We have synthesized several new N-nitroso compounds, namely N-nitrosophenacetin, N-nitrosoacetaminophen and N-nitroso-2- acetylaminofluorene(NO-AAF). The chemical structures of these compounds were characterized by spectrometric analysis of their naphthol-coupling derivatives. The new compounds are highly mutagenic to Salmonella tester strains TA 97, TA 98, TA 100 and TA 1538 and require no microsomal metabolic activation. NO-AAF in TA 98 is more mutagenic than MNNG and N-acetoxy-AAF. The teratogenic potentials of NO-AAF and N-nitrosophenacetin were studied with white Leghorn chick embryo. A high incidence of flaccid paralysis of the legs and a low incidence of feather, claw and bill malformations were found in the treated group; no such malformed embryos were found in the control group. Both N-nitrosophenacetin and NO-AAF are strong electrophiles and react readily with amino acids, nucleosides, nucleic acids and proteins at neutral pH. Our data indicated that NO-AAF is a directly acting hepatocarcinogen in Sprague-Dawley rats. NO-AAF seems to be a directly acting mutagen, teratogen and probably a carcinogen of new prototype.
- 英文摘要: --
- 中文關鍵字: Mutagen; Carcinogen; Phenacetin; Acetaminophen; 2-Acetylaminofluorene
- 英文關鍵字: 突變劑;致癌物;非那西汀;對乙醯氨基酚