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Titolo:
High levels of endogenous DNA adducts (I-compounds) in pig liver Modulation by high cholesterol high fat diet
Autore:
Vulimiri, SV; Zhou, GD; Randerath, K; Randerath, E;
Indirizzi:
Baylor Coll Med, Dept Pharmacol, Div Toxicol, Houston, TX 77030 USA BaylorColl Med Houston TX USA 77030 , Div Toxicol, Houston, TX 77030 USA
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 2, volume: 422, anno: 1998,
pagine: 297 - 311
SICI:
1386-1964(199812)422:2<297:HLOEDA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPRAGUE-DAWLEY RATS; POST-LABELING ANALYSIS; CALORIC RESTRICTION; RENAL DNA; TUMORS; LIPIDS; KIDNEY; DAMAGE; MICE; ACID;
Keywords:
I-compound; DNA adduct; oxidative stress; pig; rat; high cholesterol high fat diet;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: Randerath, K Baylor Coll Med, Dept Pharmacol, Div Toxicol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Houston, TX 77030 USA
Citazione:
S.V. Vulimiri et al., "High levels of endogenous DNA adducts (I-compounds) in pig liver Modulation by high cholesterol high fat diet", MUT RES-F M, 422(2), 1998, pp. 297-311

Abstract

I (indigenous)-compounds are bulky endogenous DNA adducts which are detected by P-32-postlabeling in unexposed animals. I-compound levels in rodents depend on age, species, strain, gender, tissue, diet, and chemical exposure. There are two classes of I-compounds, type I and type II. While many typeI I-compounds may not reflect DNA damage, type II I-compounds have been identified as oxidative DNA lesions some of which can be produced in vitro under Fenton reaction conditions. In rats, caloric restriction (CR) increasesthe levels of many type I I-compounds compared with ad Libitum fed animals, while high fat diet has the opposite effect. Here, we have tested whetherhepatic DNA of a non-rodent mammal, the pig, contains I-compounds and whether feeding a high cholesterol/high fat (HC/HF) diet modulates their levels, assuming this would affect the formation of lipid-related precursors and cause oxidative stress. Male Yorkshire pigs aged 2 months old, were fed either control or HC/HF diet (control diet supplemented with 2% cholesterol and 19% lard) for 2 months. Pig Liver DNA contained at least 19 type I and five type II I-compounds. Among the former, only five matched corresponding spots in rat liver DNA, while all the latter DNA lesions were detected in both species. The levels of both types of DNA modifications were six to eight-fold higher in pig DNA. HC/HF diet reduced levels of many type I I-compounds up to several fold but had little effect on the oxidative lesions. Several type I I-compounds showed negative linear correlations with serum cholesterol levels, while this association was positive for total type II I-compounds. The substantially elevated steady-state levels of bulky endogenous DNA adducts in the species with the longer life expectancy were surprising. Thus, for the first time, an intimate link between nutritional status and endogenous DNA modifications has been established in a non-rodent system. We propose that in order to explain our observations, differences in diet composition, antioxidant defenses, and DNA repair, as well as cytochrome P450 modulation of precursor levels and hormonal effects need to be considered. (C) 1998 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 27/11/20 alle ore 22:02:28