Induction of presumed somatic gene mutations in mice by 2-naphthylamine

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2-Naphthylamine (2-NA) is a bladder carcinogen in humans and also a proven carcinogen in mouse, hamster, dog, monkey (IARC Monograph, 1974) and rat (Radomski, 1979). It was selected as one of the well-studied carcinogens for the National Cancer Institute collaborative studies on mutagenesis as a prescreen for chemical carcinogens (Poirier and Weisburger, 1979) and for similar programmes in Japan (Kawachi et al., 1980) and the United Kingdom (Purchase et al., 1976), as well as for the extensive international Collaborative Programme for the Evaluation of Short-Term Tests for Carcinogenicity (de Serres and Ashby, 1981). After a critical appraisal of test results and test procedures it was concluded, in the Collaborative Programme, that 2-NA exhibits mutagenicity in the microbial assays and the mammalian systems, in vitro, other than that with specific loci in CHO cells. The yeast assays yielded controversial results: 4 assays indicated mutagenicity, 4 gave negative responses. In the assays in vivo, 2-NA was positive in the sex-linked recessive lethal assay with Drosophila melanogaster, but failed to induce sisterchromatid exchanges in the mouse. In the micronucleus test and sperm-abnormality assay with mice the results were inconclusive (Ashby, 1981). Few other data exist about the mutagenic effects of 2-NA in whole organisms: it induces DNA fragmentation in rat or mouse liver after treatment in vivo (Parodi et al., 1981; 1982) and is mutagenic in Drosophila when male larvae are treated (Vogel et al., 1983), but it induces neither chromosome aberrations in bone-marrow cells of rats nor mutations in the silk-worm (Kawachi et al., 1980). The genetic effects of naphthylamines have been reviewed by Mayer (1982).