TY - JOUR
T1 - Spontaneous mutation frequency and pattern in Big Blue® mice fed a vitamin E-supplemented diet
AU - Moore, Stephen R.
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 - Oxidative DNA damage
KW - Spontaneous mutation
KW - Vitamin E
KW - lacl transgene
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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
SN - 0893-6692
VL - 34
SP - 195
EP - 200
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
IS - 2-3
ER -