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Mediated Mutagenesis of Dimethylnitrosamine in Neurospora crassa by Various Metabolic Activation Systems

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Four metabolic activation systems (growth mediated, mycelium extract mediated, host mediated, and organ homogenate mediated) were used to study the mutagenic activity of dimethylnitrosamine (DMN) in both forward and reverse mutation systems in the ad-3 (adenine-3) region of Neurospora crassa. DMN was not mutagenic in Neurospora if conidia alone were treated. It was highly mutagenic, however, if conidia were treated with this compound under any of the four activation systems. Quantitative differences in DMN-induced mutation frequencies were observed between in vivo (growth and host mediated) and in vitro (mycelium extract and organ homogenate mediated) activations. The efficiency of the conversion of DMN to a mutagenic metabolite by the organs of rats and mice appeared to be in a reversed order between the host-mediated (liver > kidney > lung) and the in vitro organ homogenate-mediated (lung > kidney > liver) assays. Inductions of reverse mutations in strain N23 indicated that DMN induces base-pair substitution in N. crassa.

¹ Present address: Cancer Research Center, Thermo Electron Corporation, Waltham, Mass.

² Present address: National Institute for Occupational Safety and Health, Morgantown, W. Va. 26505. To whom requests for reprints should be addressed.

Received 9/13/78. Accepted 2/ 8/79.