Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E-supplemented diet.

T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.
(Copyright 1999 Wiley-Liss, Inc.) -->
Grant Information: R01-NS33354 United States NS NINDS NIH HHS
Substance Nomenclature: 1406-18-4 (Vitamin E)
Entry Date(s): Date Created: 19991026 Date Completed: 19991119 Latest Revision: 20071114
Update Code: 20221213
PMID: 10529744
Autor: Moore SR; Environmental Toxicology Graduate Program, University of California, Riverside, California, USA., Hill KA, Heinmoller PW, Halangoda A, Kunishige M, Buettner VL, Graham KS, Sommer SS
Jazyk: angličtina
Zdroj: Environmental and molecular mutagenesis [Environ Mol Mutagen] 1999; Vol. 34 (2-3), pp. 195-200.
Abstrakt: Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue((R)) mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-alpha-tocopherol acetate from conception until 3 months of age. Using the standard Big Blue((R)) protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacI transgene. The alpha-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C --> T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.
(Copyright 1999 Wiley-Liss, Inc.)
Databáze: MEDLINE
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