||Mutagenicity of Actinomycin D in Mammalian Cells Due to Clastogenic Effects.
DeMarini, D. M. ;
Brock, K. H. ;
Doerr, C. L. ;
Moore, M. M. ;
||Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC.
Actinomycin D ;
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Actinomycin D was clastogenic and mutagenic in L5178Y/TK+/- -3.7.2C mouse lymphoma cells. The majority of the mutants were small colonies, indicating that actinomycin D acts primarily by a clastogenic mechanism. The authors have been studying the mutagenicity of a series of agents that are highly clastogenic and induce DNA breaks but that are not mutagenic (or give very low mutant frequencies) in prokyrotic systems and at functionally heterozygous tk locus and prt) in mammalian cells. They have been evaluating agents such as actinoycin D at the functionally heterozygous tk locus in L5178Y/TK+/- -3.7.2.C mouse lymphoma cells to determine if these agents, which induce low mutant frequencies at the hemizygous hprt locus, might induce high mutant frequencies at the heterozygous tk locus. L5178Y/TK+/- -3.7.2.C mouse lymphoma cells permit the measurement of forward mutation at the functionally heterozygous tk locus, and extensive studies indicate that these cells may detect both single-gene (intragenic) mutations as well as chromosomal mutations (intragenic events resulting from chromosomal rearrangements and/or functional multilocus deletions) affecting the expression of the tk locus.