The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and US NTP

The genotoxicity of 30 aromatic amines selected from IARC (International Ag ency for Research on Cancer) groups I, 2A, 2B and 3 and from the U.S. NTP ( National Toxicology Program) carcinogenicity database were evaluated using the alkaline single cell gel electrophoresis (SCG) (Comet) assay in mouse o rgans. We treated groups of four mice once orally at the maximum tolerated dose (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow 3, 8 and 24 h after treatment. For the 20 aromatic amines that are rodent carcinogens, the assay was positive in at least one organ, suggesting a high predictive ability for the assay. For most of the SCG-pos itive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, i n contrast, for the target organs not to show DNA damage. Organ-specific ge notoxicity, therefore, is necessary but not sufficient for the prediction o f organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amin es (eight were Ames test-positive and two were Ames test-negative), the ass ay was negative in all organs studied. In the safety evaluation of chemical s, it is important to demonstrate that Ames test-positive agents are not ge notoxic in vivo. Chemical carcinogens can be classified as genotoxic (Ames test-positive) and putative non-genotoxic (Ames test-negative) carcinogens. The alkaline SCG assay, which detects DNA lesions, is not suitable for ide ntifying non-genotoxic carcinogens. The present SCG study revealed a high p ositive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic non-carcinogens. These results suggest that the alkaline SCG assay can be usefully used to evaluate the in vivo g enotoxicity of chemicals in multiple organs, providing for a good assessmen t of potential carcinogenicity. (C) 1999 Elsevier Science B.V. All rights r eserved.