Mutation induction by mechanical irritation caused by uracil-induced urolithiasis in Big Blue (R) rats

Citation
S. Takahashi et al., Mutation induction by mechanical irritation caused by uracil-induced urolithiasis in Big Blue (R) rats, MUT RES-F M, 447(2), 2000, pp. 275-280
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
ISSN journal
1386-1964 → ACNP
Volume
447
Issue
2
Year of publication
2000
Pages
275 - 280
Database
ISI
SICI code
1386-1964(20000214)447:2<275:MIBMIC>2.0.ZU;2-9
Abstract
Some chronic mechanical irritations induce cancers, and it is speculated th at mutations are induced by increased rate of cell proliferation caused by the irritation. In this study, it was investigated using chronic mechanical irritation to urothelium caused by urolithiasis, whether mutations are rea lly induced by such cell proliferation or not. Male rats transgenic for lac I (Big Blue(R) rats), in which lacI mutations accumulated in tissue can be measured, were fed 3% uracil, a component of RNA, to induce urolithiasis as sociated with papillomatosis, and eventually with bladder cancers. The freq uency of independent mutations in the bladders of the treated rats showed 3 -5 fold increases at weeks 10, 20, and 51 (P = 0.01 at week 51) while the f requency was not elevated at week 2. The mutation frequencies in the contro l bladders ranged from 3 to 9 x 10(-6). In both groups, G to A transitions at CpG sites, indicative of spontaneous mutations, constituted the most pre valent mutations. Mechanical irritation caused by uracil was shown to induc e a 3-5 fold increase of mutations, possibly through an elevation of sponta neous mutations by vigorous cell proliferation. (C) 2000 Elsevier Science B .V. All rights reserved.