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Titolo:
Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies
Autore:
Ishikawa, T; Ide, F; Qin, XS; Zhang, SM; Takahashi, T; Sekiguchi, M; Tanaka, K; Nakatsuru, Y;
Indirizzi:
Univ Tokyo, Fac Med, Dept Pathol, Bunkyo Ku, Tokyo 1130033, Japan Univ Tokyo Tokyo Japan 1130033 t Pathol, Bunkyo Ku, Tokyo 1130033, Japan Fukuoka Dent Coll, Dept Biol, Fukuoka 8140175, Japan Fukuoka Dent Coll Fukuoka Japan 8140175 ept Biol, Fukuoka 8140175, Japan Osaka Univ, Inst Med & Cellular Biol, Suita, Osaka 5650871, Japan Osaka Univ Suita Osaka Japan 5650871 ar Biol, Suita, Osaka 5650871, Japan
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 477, anno: 2001,
pagine: 41 - 49
SICI:
1386-1964(20010602)477:1-2<41:IODRIC>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEOTIDE EXCISION-REPAIR; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ACTIVITY; XERODERMA-PIGMENTOSUM PATIENTS; ESCHERICHIA-COLI; MICE LACKING; SKIN-CANCER; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; INDUCED TUMORIGENESIS; ULTRAVIOLET-B; LIVER-TUMORS;
Keywords:
DNA repair; transgenic mice; knockout mice; chemical carcinogenesis; O-6-methylguanine-DNA methyltransferase; nucleotide excision repair;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Ishikawa, T Fac Univ Evaluat & Res, Natl Inst Acad Degrees, Chiyoda Ku, 2-1-2 Hitotsubashi, Tokyo 1010003, Japan Fac Univ Evaluat & Res 2-1-2 Hitotsubashi Tokyo Japan 1010003
Citazione:
T. Ishikawa et al., "Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies", MUT RES-F M, 477(1-2), 2001, pp. 41-49

Abstract

We have generated transgenic mice by introducing copies of the E. coli O-6-methylguanine-DNA methyltransferase gene, ada. Liver extracts from homozygotes demonstrate about three times the control enzyme activity and increaseup to about eight-fold can be induced by treatment with zinc, since the metal-responsive metallothionein promoter is attached to the ada gene. Furthermore, studies of liver carcinogenesis in our transgenic mice demonstrated significantly reduced rates of development of hepatocellular tumors after treatment with dimethylnitrosamine or diethylnitrosamine. It is well known that xeroderma pigmentosum (XP) patients are deficient inDNA repair. The availability of XPA (XP group A complementing) knockout mice has enabled us to investigate the functional role of the XPA nucleotide excision repair gene in carcinogenesis in vivo, first using the mouse skin as a model system. XPA-/- mice demonstrated skin ulcers 5-7 days after 7,12-dimethylbenz[a]anthracene (DMBA) treatment and papilloma development within 4 weeks prior to promotion, skin tumor incidence being also much higher than in heterozygous and wild-type mice. Experiments targeting the lung, liver and tongue have also been conducted to answer the question of whether the internal organs of these mice are also susceptible to chemical carcinogens. For lung carcinogenesis, mice were instilled intratracheally with a small dose of benzo[a]pyrene. The pulmonary tumor incidence in XPA-/- mice was significantly higher than in XPA+/- and XPA+/+ mice. XPA-/- mice were also found to be have enhanced sensitivity to aflatoxin B-1 regarding liver tumor induction, In addition, administration of 4-nitroquinoline-1-oxide in drinking water for 50 weeks resulted in tongue tumors only in XPA-/- mice. These studies, thus, provided convincing evidence that XPA mice are also sensitive to carcinogenesis in organs other than the skin. (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 10/07/20 alle ore 01:44:57