The comet assay in eight mouse organs: results with 24 azo compounds

The genotoxicity of 24 azo compounds selected from IARC (International Agen cy for Research on Cancer) groups 2A, 2B, and 3 were determined by the come t (alkaline single cell gel electrophoresis, SCG) assay in eight mouse orga ns. We treated groups of four mice once orally at the maximum tolerated dos e (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, an d bone marrow 3, 8, and 24 h after treatment, For the 17 azo compounds, the assay was positive in at least one organ; (1) 14 and 12 azo compounds indu ced DNA damage in the colon and liver, respectively, (2) the genotoxic effe ct of mast of them was greatest in the colon, and (3) there were high posit ive responses in the gastrointestinal organs, but those organs are not targ ets for carcinogenesis. One possible explanation for this discrepancy is th at the assay detects DNA damage induced shortly after administration of a r elatively high dose, while carcinogenicity is detected after long treatment with relatively low doses. The metabolic enzymes may become saturated foll owing high doses and the rates and pathways of metabolic activation and det oxification may differ following high;single doses vs. low long-term doses. Furthermore, considering that spontaneous colon tumors are very rare in ra ts and mice, the ability to detect tumorigenic effects in the colon of thos e animals might be lower than the ability to detect genotoxic events in the comet assay. The in vivo comet assay, which has advantage of reflecting te st chemical absorption, distribution, and excretion as well as metabolism s hould be effective for estimating the risk posed by azo dyes to humans in s pite of the difference in dosage regimen. (C) 2000 Elsevier Science B.V. Al l rights reserved.