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Titolo:
Effects of arsenite on p53, p21 and cyclin D expression in normal human fibroblasts - a possible mechanism for arsenite's comutagenicity
Autore:
Vogt, BL; Rossman, TG;
Indirizzi:
NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Park, NY 10987 USA NYU Tuxedo Park NY USA 10987 Inst Environm Med, Tuxedo Park, NY 10987 USA NYU, Sch Med, Kaplan Canc Ctr, Tuxedo Park, NY 10987 USA NYU Tuxedo Park NY USA 10987 , Kaplan Canc Ctr, Tuxedo Park, NY 10987 USA
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 478, anno: 2001,
pagine: 159 - 168
SICI:
1386-1964(20010701)478:1-2<159:EOAOPP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN CANCER-CELLS; NUCLEOTIDE EXCISION-REPAIR; CHINESE-HAMSTER CELLS; C-MYC EXPRESSION; WILD-TYPE P53; SODIUM ARSENITE; NITRIC-OXIDE; CYTO-TOXICITY; DNA-REPAIR; ENDOTHELIAL-CELLS;
Keywords:
arsenic; comutagenesis; fibroblasts; p53; p21; cyclin D;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
79
Recensione:
Indirizzi per estratti:
Indirizzo: Rossman, TG NYU, Sch Med, Nelson Inst Environm Med, 57 Old Forge Rd, Tuxedo Park, NY 10987 USA NYU 57 Old Forge Rd Tuxedo Park NY USA 10987 ark, NY 10987 USA
Citazione:
B.L. Vogt e T.G. Rossman, "Effects of arsenite on p53, p21 and cyclin D expression in normal human fibroblasts - a possible mechanism for arsenite's comutagenicity", MUT RES-F M, 478(1-2), 2001, pp. 159-168

Abstract

Arsenite, the most likely environmental carcinogenic form of arsenic, is not significantly mutagenic at non-toxic concentrations, but is able to enhance the mutagenicity of other agents. Evidence suggests that this comutagenic effect of arsenite is due to inhibition of DNA repair, but no specific repair enzyme has been found to be sensitive to low (<1 muM) concentrations of arsenite. To determine whether arsenite affects signaling which might alter DNA repair, this study assesses the effect of arsenite on p53-related signal transduction pathways after ionizing radiation. Long-term (14 day) low dose (0.1 muM) arsenite caused a modest increase in p53 expression in WI38 normal human fibroblasts, while only toxic (50 muM) concentrations increased p53 levels after short-term (18 h) exposure. When cells were irradiated(6 Gy), p53 and p21 protein concentrations were increased after 4 h, as expected. Both long-term, low dose and short-term, high dose exposure to arsenite greatly suppressed the radiation-induced increase in p21 abundance. Inaddition, long-term, low dose (but not short-term, high dose) exposure to arsenite resulted in increased expression of cyclin D1. These results show that in cells treated with arsenite, p53-dependent increase in p21 expression, normally a block to cell cycle progression after DNA damage, is deficient. At the same time, low (non-toxic) exposure to arsenite enhances positive growth signaling. We suggest that the absence of normal p53 functioning, along with increased positive growth signaling in the presence of DNA damage may result in defective DNA repair and account for the comutagenic effects of arsenite. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 18:49:21