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

Stephen Moore, Kathleen A. Hill, Petra W. Heinmoller, Asanga Halangoda, Makoto Kunishige, Victoria L. Buettner, Kenneth S. Graham, Steve S. Sommer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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® 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,1-α- tocopherol acetate from conception until 3 months of age. Using the standard Big Blue® 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 lacl transgene. The α-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- α-tocopherol acetate.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalEnvironmental and Molecular Mutagenesis
Volume34
Issue number2-3
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Mutation Rate
Nutrition
vitamin
Vitamin E
mutation
diet
Diet
Tissue
DNA Damage
Adipose Tissue
alpha-Tocopherol
DNA
damage
acetate
Thymus
Mutation
Tocopherols
Chemoprevention
tissue
Transgenes

Keywords

  • Antioxidants
  • Diet
  • lacl transgene
  • Oxidative DNA damage
  • Spontaneous mutation
  • Vitamin E

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Spontaneous mutation frequency and pattern in Big Blue® mice fed a vitamin E-supplemented diet. / Moore, Stephen; Hill, Kathleen A.; Heinmoller, Petra W.; Halangoda, Asanga; Kunishige, Makoto; Buettner, Victoria L.; Graham, Kenneth S.; Sommer, Steve S.

In: Environmental and Molecular Mutagenesis, Vol. 34, No. 2-3, 1999, p. 195-200.

Research output: Contribution to journalArticle

Moore, Stephen ; Hill, Kathleen A. ; Heinmoller, Petra W. ; Halangoda, Asanga ; Kunishige, Makoto ; Buettner, Victoria L. ; Graham, Kenneth S. ; Sommer, Steve S. / Spontaneous mutation frequency and pattern in Big Blue® mice fed a vitamin E-supplemented diet. In: Environmental and Molecular Mutagenesis. 1999 ; Vol. 34, No. 2-3. pp. 195-200.
@article{37363703a56743e39aad425f06d418c4,
title = "Spontaneous mutation frequency and pattern in Big Blue{\circledR} mice fed a vitamin E-supplemented diet",
abstract = "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{\circledR} 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,1-α- tocopherol acetate from conception until 3 months of age. Using the standard Big Blue{\circledR} 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 lacl transgene. The α-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- α-tocopherol acetate.",
keywords = "Antioxidants, Diet, lacl transgene, Oxidative DNA damage, Spontaneous mutation, Vitamin E",
author = "Stephen Moore and Hill, {Kathleen A.} and Heinmoller, {Petra W.} and Asanga Halangoda and Makoto Kunishige and Buettner, {Victoria L.} and Graham, {Kenneth S.} and Sommer, {Steve S.}",
year = "1999",
doi = "10.1002/(SICI)1098-2280(1999)34:2/3<195::AID-EM19>3.0.CO;2-I",
language = "English (US)",
volume = "34",
pages = "195--200",
journal = "Environmental and Molecular Mutagenesis",
issn = "0893-6692",
publisher = "Wiley-Liss Inc.",
number = "2-3",

}

TY - JOUR

T1 - Spontaneous mutation frequency and pattern in Big Blue® mice fed a vitamin E-supplemented diet

AU - Moore, Stephen

AU - Hill, Kathleen A.

AU - Heinmoller, Petra W.

AU - Halangoda, Asanga

AU - Kunishige, Makoto

AU - Buettner, Victoria L.

AU - Graham, Kenneth S.

AU - Sommer, Steve S.

PY - 1999

Y1 - 1999

N2 - 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® 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,1-α- tocopherol acetate from conception until 3 months of age. Using the standard Big Blue® 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 lacl transgene. The α-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- α-tocopherol acetate.

AB - 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® 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,1-α- tocopherol acetate from conception until 3 months of age. Using the standard Big Blue® 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 lacl transgene. The α-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- α-tocopherol acetate.

KW - Antioxidants

KW - Diet

KW - lacl transgene

KW - Oxidative DNA damage

KW - Spontaneous mutation

KW - Vitamin E

UR - http://www.scopus.com/inward/record.url?scp=0032743265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032743265&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2280(1999)34:2/3<195::AID-EM19>3.0.CO;2-I

DO - 10.1002/(SICI)1098-2280(1999)34:2/3<195::AID-EM19>3.0.CO;2-I

M3 - Article

C2 - 10529744

AN - SCOPUS:0032743265

VL - 34

SP - 195

EP - 200

JO - Environmental and Molecular Mutagenesis

JF - Environmental and Molecular Mutagenesis

SN - 0893-6692

IS - 2-3

ER -