Cyanoethylation of DNA in Vivo by 3-(Methylnitrosamino)propionitrile, an Areca-aeri\ed Carcinogen1
نویسندگان
چکیده
2-Cyanoethyldiazohydroxide is a likely product of metabolic a-hydroxylation of 3-(methylnitrosamino)propionitrile(MNPN). The reaction of 2-{Ar-carbethoxy-/V-nitrosamino)propionitrile, a stable precursor of 2cyanoethyldiazohydroxide, with deoxyguanosine, catalyzed by porcine liver esterase, was investigated. Two major deoxyguanosine adducts were produced. They were isolated by high-performance liquid chromatography and characterized by their UV spectra, mass spectra, and proton magnetic resonance spectra. On the basis of these spectral data, the structures of the two adducts were assigned as 7-(2-cyanoethyl)guanine and 0'-(2-cyanoethyl)deoxyguanosine. The potential of MNPN to cyanoethylate DNA in F344 rats was evaluated by measuring 7-(2-cyanoethyl)guanine and 0'-(2-cyanoethyl)guanine in the liver, nasal mucosa, and esophagus. The highest levels were detected in the nasal cavity, which is one of the major target organs for the carcinogenic effects of MNPN.
منابع مشابه
Cyanoethylation of DNA in vivo by 3-(methylnitrosamino)propionitrile, an Areca-derived carcinogen.
2-Cyanoethyldiazohydroxide is a likely product of metabolic alpha-hydroxylation of 3-(methylnitrosamino)propionitrile (MNPN). The reaction of 2-(N-carbethoxy-N-nitrosamino)propionitrile, a stable precursor of 2-cyanoethyldiazohydroxide, with deoxyguanosine, catalyzed by porcine liver esterase, was investigated. Two major deoxyguanosine adducts were produced. They were isolated by high-performan...
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