The comet assay in eight mouse organs: results with 24 azo compounds.
The genotoxicity of 24 azo compounds selected from IARC (International Agency for Research on Cancer) groups 2A, 2B, and 3 were determined by the comet (alkaline single cell gel electrophoresis, SCG) assay in eight mouse organs. 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 17 azo compounds, the assay was positive in at least one organ; (1) 14 and 12 azo compounds induced DNA damage in the colon and liver, respectively, (2) the genotoxic effect of most of them was greatest in the colon, and (3) there were high positive responses in the gastrointestinal organs, but those organs are not targets for carcinogenesis. One possible explanation for this discrepancy is that the assay detects DNA damage induced shortly after administration of a relatively high dose, while carcinogenicity is detected after long treatment with relatively low doses. The metabolic enzymes may become saturated following high doses and the rates and pathways of metabolic activation and detoxification may differ following high single doses vs. low long-term doses. Furthermore, considering that spontaneous colon tumors are very rare in rats and mice, the ability to detect tumorigenic effects in the colon of those 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 test chemical absorption, distribution, and excretion as well as metabolism, should be effective for estimating the risk posed by azo dyes to humans in spite of the difference in dosage regimen.
Tsuda
S
S
Laboratory of Veterinary Public Health, Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Ueda 3-18-8, Morioka, Japan.
Matsusaka
N
N
Madarame
H
H
Ueno
S
S
Susa
N
N
Ishida
K
K
Kawamura
N
N
Sekihashi
K
K
Sasaki
Y F
YF
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004586:Electrophoresis; D006801:Humans; D008297:Male; D051379:Mice; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D014018:Tissue Distribution
D001391:Azo Compounds; D009153:Mutagens