Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
PYRIDYLOXOBUTYL DNA ADDUCTS INHIBIT THE REPAIR OF O(6)-METHYLGUANINE
Autore:
PETERSON LA; LIU XK; HECHT SS;
Indirizzi:
AMER HLTH FDN,DIV CHEM CARCINOGENESIS VALHALLA NY 10595
Titolo Testata:
Cancer research
fascicolo: 12, volume: 53, anno: 1993,
pagine: 2780 - 2785
SICI:
0008-5472(1993)53:12<2780:PDAITR>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOBACCO-SPECIFIC NITROSAMINE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ACTIVITY; MASS-SPECTROMETRIC ANALYSIS; CHEMICAL CARCINOGENESIS; RAT-LIVER; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALPHA-HYDROXYLATION; HEMOGLOBIN ADDUCTS; ALKYLATING-AGENTS; F344 RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
L.A. Peterson et al., "PYRIDYLOXOBUTYL DNA ADDUCTS INHIBIT THE REPAIR OF O(6)-METHYLGUANINE", Cancer research, 53(12), 1993, pp. 2780-2785

Abstract

The carcinogenic tobacco-specific nitrosamine, (methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), both methylates and pyridyloxobutylates DNA. O6-Methylguanine (O6-mG) persistence has been correlated to NNK-induced lung tumor formation in A/J mice. The pyridyloxobutylation pathway enhances the tumorigenicity of the methylation pathway. In this paper we test the hypothesis that DNA pyridyloxobutylation increases O6-mG persistence by inhibiting the repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Pyridyloxobutylated DNA was generated by reactingcalf thymus DNA with the model pyridyloxobutylating agent acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) in the presence of esterase. The alkylated DNA inhibited the ability or partially purified rat liver AGT to repair O6-mG when it was incubated with AGT prior to the addition of H-3-methylated DNA. The extent of inhibition was dependent on the amount of NNKOAc reacted with DNA. The ability of NNKOAc-treated DNA to inhibit AGT was destroyed when the DNA was subjected to neutral thermal hydrolysis. Approximately 1 pmol of AGT was inhibited for every 25 to 50 pmol of 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing adducts present in NNKOAc-treated DNA. The inhibitory activity of this alkylated DNA was relatively stable under physiological conditions (pH 7.4, 37-degrees-C). Only 13% of the AGT reactive activity was lostafter 7 days. When pyridyloxobutylated DNA was incubated simultaneously with H-3-methylated DNA and AGT, a significant reduction in [H-3]methyl transfer to AGT was observed. The levels of reduction were similar to those observed when unlabeled methylated DNA containing comparable levels of O6-mG was substituted for NNKOAc-treated DNA. Based on these results, a cocarcinogenic role for pyridyloxobutylation in NNK-induced lung tumorigenesis is proposed in which pyridyloxobutyl DNA adduct(s) compete with O6-mG for reaction with AGT resulting in sustained levels of O6-mG. These enhanced levels then increase the probability of tumor induction by NNK.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:27:09