当前位置： SCI文献检索 > ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY期刊下所有文献 > Altered BRCA1 and BRCA2 responses and mutation of BRCA1 gene in mice exposed chronically and transgenerationally to aqueous extract of betel nut (AEBN).

Altered BRCA1 and BRCA2 responses and mutation of BRCA1 gene in mice exposed chronically and transgenerationally to aqueous extract of betel nut (AEBN).

Abstract：

:The Brca1 and Brca2 tumor suppressor genes are involved in the maintenance of genomic integrity as they facilitate error free DNA repair. This study was designed to understand the role of Brca1 and Brca2 in betel nut (BN) induced chronic and transgenerational carcinogenesis in mice. Young male and female Swiss Albino mice were chronically as well as transgenerationally exposed to aqueous extract of betel nut (AEBN) in drinking water (2 mg ml(-1)) for up to 24 weeks. In chronically exposed mice, the levels of Brca1 and Brca2 proteins were elevated to approximately 1.4-fold over the age matched controls after 2 weeks of exposure to AEBN, followed by a decline below the controls. In transgenerationally exposed mice, both Brca1 and Brca2 proteins remained below the controls from the onset of AEBN exposure and rapidly declined further, indicating a loss of tumor suppressor protection. Nucleotide sequencing of exon 11 of Brca1 and exon 27 of Brca2 did not reveal mutation in liver nodules of chronically exposed mice, while a G → C mutation Brca1 was observed in liver nodules as well as in solid tumors developing in transgenerationally exposed mice. Thus, the genomic instability arising due to the lowering in the levels of Brca1 and Brca2 proteins and mutation in exon 11 of Brca1 gene contributed to the increased risk of cancer in mice exposed transgenerationally to AEBN.

journal_name

Environ Toxicol Pharmacol

journal_title

Environmental toxicology and pharmacology

authors

Choudhury Y,Sharan RN

doi

10.1016/j.etap.2010.09.006

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

57-69

issue

1

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(10)00148-1

journal_volume

31

pub_type

杂志文章

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