Tandem-base mutations occur in mouse liver and adipose tissue preferentially as G:C to T:A transversions and accumulate with age.

Tandem-base mutations (TBM) are associated with ultraviolet light and other mutagens. Herein, we report an age- and tissue-specific difference in the frequency of spontaneous TBM in Big Blue transgenic mice. A total of 390 mutants from liver and adipose tissue contained 17 and 4 TBM, respectively, while no TBM were detected in 683 mutants from six other tissues. There was a proportional increase in the frequency of TBM in liver with age (29 days postconception to 25 months of age). Nine TBM (43%) were GG to TT transversions that preferentially occurred at specific sites. The remaining 12 mutants contained at least one transversion mutation each. We speculate that the increase of TBM in liver and adipose tissue with age is due to chronic mutagen exposure, perhaps derived from fat in the diet. Copyright 1999 Wiley-Liss, Inc.