The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP.
The genotoxicity of 30 aromatic amines selected from IARC (International Agency for Research on Cancer) groups 1, 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 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 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-positive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Organ-specific genotoxicity, therefore, is necessary but not sufficient for the prediction of organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amines (eight were Ames test-positive and two were Ames test-negative), the assay was negative in all organs studied. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic 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 identifying non-genotoxic carcinogens. The present SCG study revealed a high positive 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 genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.
Sasaki
Y F
YF
Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology, Tamonoki Uwanotai 16-1, Hachinohe, Aomori 039-11, Japan. yfsasaki-c@hachinohe-ct.ac.jp
Fujikawa
K
K
Ishida
K
K
Kawamura
N
N
Nishikawa
Y
Y
Ohta
S
S
Satoh
M
M
Madarame
H
H
Ueno
S
S
Susa
N
N
Matsusaka
N
N
Tsuda
S
S
D000588:Amines / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000633:toxicity*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009316:National Institutes of Health (U.S.); D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014481:United States
D000588:Amines; D002273:Carcinogens; D006841:Hydrocarbons, Aromatic; D009153:Mutagens; D004247:DNA