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Titolo:
Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells
Autore:
Sharma, RA; Gescher, A; Plastaras, JP; Leuratti, C; Singh, R; Gallacher-Horley, B; Offord, E; Marnett, LJ; Steward, WP; Plummer, SM;
Indirizzi:
Univ Leicester, Dept Oncol, Leicester LE1 9HN, Leics, England Univ Leicester Leicester Leics England LE1 9HN er LE1 9HN, Leics, England Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England Univ Leicester Leicester Leics England LE1 9HN er LE1 9HN, Leics, England Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA Vanderbilt Ingram CancCtr Nashville TN USA 37232 Nashville, TN 37232 USA Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland Nestle Res Ctr LausanneSwitzerland 26 CH-1000 Lausanne 26, Switzerland
Titolo Testata:
CARCINOGENESIS
fascicolo: 9, volume: 22, anno: 2001,
pagine: 1557 - 1560
SICI:
0143-3334(200109)22:9<1557:CMAPAO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROSTAGLANDIN-G/H SYNTHASE-1; LIPID-PEROXIDATION; DNA-DAMAGE; SELECTIVE-INHIBITION; COLORECTAL-CANCER; EXPRESSION; LIVER; ASSAY; ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Sharma, RA Univ Leicester, Dept Oncol, Leicester LE1 9HN, Leics, England Univ Leicester Leicester Leics England LE1 9HN Leics, England
Citazione:
R.A. Sharma et al., "Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine in human colon cells", CARCINOGENE, 22(9), 2001, pp. 1557-1560

Abstract

Cyclooxygenases (COX) catalyse the oxygenation of arachidonic acid to prostaglandin (PG) endoperoxides. Activity of one of the COX isoforms, COX-2, results in production of prostaglandin E-2 (PGE(2)) via the endoperoxide PGH(2). COX-2 has been implicated in the pathogenesis of colorectal cancer. Malondialdehyde (MDA) is a mutagen produced by spontaneous and enzymatic breakdown of PGH(2). MDA reacts with DNA to form adducts, predominantly the pyrimidopurinone adduct of deoxyguanosine (M(1)G). Here the hypothesis was tested that COX-2 activity in human colon cells results in formation of MDA and generation of M(1)G adducts. M(1)G was detected in basal cultures of human non-malignant colon epithelial (HCEC) and malignant SW48, SW480, HT29 andHCA-7 colon cells, at levels from 77 to 148 adducts/10(8) nucleotides. Only HCA-7 and HT29 cells expressed COX-2 protein. Levels of M(1)G correlated significantly (r = 0.98, P < 0.001) with those of intracellular MDA determined colorimetrically in the four malignant cell types, but neither parameter correlated with expression of COX-2 or PG biosynthesis. Induction of COX-2 expression by phorbol 12-myristate 13-acetate in HCEC cells increased PGE(2) production 20-fold and MDA concentration 3-fold. Selective inhibition of COX-2 activity in HCA-7 cells by NS-398 significantly inhibited PGE2 production, but altered neither MDA nor M(1)G levels. Malondialdehyde treatmentof HCEC cells resulted in a doubling of MIG levels. These results show forthe first time in human colon cells that COX-2 activity is associated withformation of the endogenous mutagen, MDA. Moreover, they demonstrate the correlation between,MDA concentration and M(1)G adduct levels in malignant cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 17:03:28