Mutagenicity and Clastogenicity of Teniposide (VM-26) in L5178Y/TK(+/-)-3.7.2C Mouse Lymphoma Cells

摘要

The antitumor drug teniposide (VM-26) is a potent inducer of DNA breaks (Long et al., Cancer Res., 45:3106, 1985), but it is only weakly mutagenic at the hprt locus in CHO cells (Singh and Gupta, Cancer Res., 43:577, 1983). In the present study, the mutagenic and clastogenic activities of teniposide were evaluated in L5178Y/TK+/- -3.7.2C mouse lymphoma cells. While not a good mutagen at the hprt locus, teniposide is a potent mutagen at the tk locus, with as little as 0.5 ng/ml producing 220 TK mutants/ten to the 6th power survivors at 96% survival (background = 100/ten to the 6th power survivors). This same dose of teniposide induced 38 aberrations per 100 metaphases (background = 7/100 cells). At 7 ng/ml, teniposide induced approximately 2,700 TK mutants/ten to the 6th power survivors at approximately 10% survival. At the highest dose sampled for aberration analysis (5 ng/ml), teniposide induced 244 aberrations/100 cells. Most of the aberrations were chromosomal rather than chromatid events. As expected for a compound acting primarily by a clastogenic mechanism, most of the TK mutants were small colonies.