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Titolo:
DNA adduct formation and molecular analysis of in vivo lacI mutations in the mammary tissue of Big Blue (R) rats treated with 7,12-dimethylbenz[a]anthracene
Autore:
Manjanatha, MG; Shelton, SD; Culp, SJ; Blankenship, LR; Casciano, DA;
Indirizzi:
US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Genet, Jefferson, AR 72079 USA US FDA Jefferson AR USA 72079 an Serv, Div Genet, Jefferson, AR 72079 USA US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Biochem Toxicol,Jefferson, AR 72079 USA US FDA Jefferson AR USA 72079 Div Biochem Toxicol,Jefferson, AR 72079 USA
Titolo Testata:
CARCINOGENESIS
fascicolo: 2, volume: 21, anno: 2000,
pagine: 265 - 273
SICI:
0143-3334(200002)21:2<265:DAFAMA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
N-RAS MUTATION; TRANSGENIC MICE; HA-RAS; MUTANT FREQUENCY; GENE; CELLS; CARCINOGENESIS; ONCOGENES; SEQUENCE; SPECTRA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Manjanatha, MG US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Genet, Jefferson, AR 72079 USA US FDA Jefferson AR USA 72079 net, Jefferson, AR 72079 USA
Citazione:
M.G. Manjanatha et al., "DNA adduct formation and molecular analysis of in vivo lacI mutations in the mammary tissue of Big Blue (R) rats treated with 7,12-dimethylbenz[a]anthracene", CARCINOGENE, 21(2), 2000, pp. 265-273

Abstract

Recently we compared the lad and Hprt mutant frequencies (MFs) and types of mutations in lymphocytes of Big Blue(R) (BB) rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA) under conditions that result in mammary gland tumors. In this study, we have examined the target mammary tissue for DMBA-induced DNA adducts, lad MF and types of lad mutations. seven-week-old female BE rats were given single doses of 0, 20 or 130 mg/kg DMBA by gavage and the DNA adducts and lad MFs in the mammary tissue were measured over a periodof 14 days and 18 weeks, respectively, following treatment, The lacI MF inthe mammary tissue increased for 10 weeks and then remained relatively constant; 130 mg/kg DMBA produced a 14-fold increase in the MF (255 +/- 50 x 10(-6) p.f.u.) over control MF (18.3 +/- 4 x 10(-6) p.f.u.). P-32-post-labeling analysis of DNA from mammary tissue and splenic lymphocytes of treated rats revealed two major adducts, Comparison of these adducts with DMBA standards indicated that the adducts formed by DMBA involved both G:C and A:T base pairs. DNA sequencing revealed that the majority of DMBA-induced lad mutations were base pair sutbstitutions and that A:T-->T:A (44% of the independent mutations) and G:C-->T:A (24% of the independent mutations:) transversions were the predominant types. Furthermore, the mutational results revealed a 'hotspot' for a G-->T mutation in codon 95 (GTG-->TTG) of the lad gene in mammary tissue. These results suggest that DMBA is highly mutagenic tolad in mammary tissue and that adducts with bath G:C and A:T base pairs participate in forming mutations in DMBA-treated BB rats.

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Documento generato il 01/06/20 alle ore 01:27:28