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

✍ Scribed by Stephen R. Moore; Kathleen A. Hill; Petra W. Heinmoller; Asanga Halangoda; Makoto Kunishige; Victoria L. Buettner; Kenneth S. Graham; Steve S. Sommer

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 58 KB
• Volume: 34
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1999)34:2/3<195::aid-em19>3.0.co;2-i

✦ Synopsis

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 highdose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-␣-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 lacI transgene. The ␣-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed lit-tle 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 ϭ 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P ϭ 0.40). When data from all tissues were combined, a reduction in G:C 3 T:A transversions was observed (P ϭ 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-␣-tocopherol acetate.