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MUTAGENESIS OF L5178Y/TK(+/-)-3.7.2C MOUSE LYMPHOMA CELLS BY THE CLASTOGEN ELLIPTICINE
Citation:
Moore, M., K. Brock, C.L. Doerr, AND D.M. DeMarini. MUTAGENESIS OF L5178Y/TK(+/-)-3.7.2C MOUSE LYMPHOMA CELLS BY THE CLASTOGEN ELLIPTICINE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-87/195 (NTIS PB88165931).
Description:
The antitumor drug ellipticine is clastogenic in CHO cells (Bhuyan et al., 1972) but is only weakly mutagenic at the hprt locus in CHO cells (DeMarini et al., 1983; Singh and Gupta, 1983a,b). 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 270 TK-deficient mutants/10 to the 6th power survivors at approx. 50% survival (background = 72/10 to the 6th power survivors). 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/10 to the 6th power survivors at approx. 10% survival and produced 242 aberrations/100 cells. 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.