Mutagenesis of L5178Y/TK+ / − −3.7.2C mouse lymphoma cells by the clastogen ellipticine

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Abstract
Ellipticine is a potent clastogen in CHO cells (Bhuyan et al: Cancer Res 32:2538–2544, 1972). The reported mutant frequencies produced by ellipticine at the hprt locus in CHO cells are ⩽50/106 survivors (background ∽ 2/106; survival = 10%) (DeMarini et al: Cancer Res 43:3544–3552, 1983; Singh and Gupta: Cancer Res 43:577–584, 1983; Environ Mutagen 5:871–880, 1983). In the present study, the mutagenic and clastogenic activities of ellipticine were evaluated in L5178Y/TK+/− −3.7.2C mouse lymphoma cells. Unlike the results at the hprt locus, ellipticine is a potent mutagen at the tk locus, with as little as 50 ng/ml producing an induced mutant frequency of 142/106 survivors (background = 56/106; survival = 61 %) and 198/106 survivors (background = 72/106; survival = 50%) in two separate experiments. This same dose of ellipticine induced 44 aberrations per 100 metaphases (background = 5/100 cells). At 400 ng/ml, ellipticine induced over 1,000 mutants /106 survivors at ∽ 10% survival and produced 242 aberrations/100 cells. Under the test conditions, most of the aberrations were chromosome rather than chromatid events. As expected for a compound acting primarily by a clastogenic mechanism, almost all of the TK-deficient mutants were small colonies. Thus, ellipticine is a potent clastogen in both Chinese hamster cells and in mouse lymphoma cells; however, it is a potent mutagen at only the tk locus and not at the hprt locus. These results support.

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