Genotoxicity of a variety of azobenzene and aminoazobenzene compounds in the hepatocyte/DNA repair test and the Salmonella/mutagenicity test.
Genotoxicity of 39 azo dye compounds of azobenzenes, aminoazobenzenes, and diaminoazobenzenes was examined in the hepatocyte primary culture/DNA repair test. Azobenzene (AzB) and 3,3'- or 4,4'-substituted azobenzenes such as (CH3)2AzB, (CH2OH)2AzB, (CH2OCOCH3)2AzB, and (CH2Cl)2AzB did not generate DNA repair, indicating lack of genotoxicity of these compounds. In contrast, all of 24 aminoazobenzenes, including those of unknown carcinogenicity, i.e., 3'-methyl-4-aminoazobenzene, 3'-CH2OH-aminoazobenzene, 3'-hydroxymethyl-N-methyl-4-aminoazobenzene, 3'-COOH-methylaminoazobenzene, 4'-formyl-N,N-dimethyl-4-aminoazobenzene, 3'-CH2Cl-dimethylaminoazobenzene, 4'-CH2Cl-dimethylaminoazobenzene, and 2'-, 3'-, or 4'-CH2OCOCH3-dimethylaminoazobenzene, elicited DNA repair synthesis. A positive DNA repair response was obtained for the 3 of 6 tested diaminoazobenzenes, i.e., N'-acetyl-N'-methyl-4-amino-dimethylaminoazobenzene, N'-acetyl-N'-methyl-4-amino-methylaminoazobenzene, and N'-acetyl-N'-methyl-4-amino-N-acetyl-methylaminoazobenzene, which are known to be carcinogenic. These results indicate that the amino group is functional for the expression of genotoxicity of azobenzene compounds. Twenty-one azobenzenes of these 3 classes were also examined for their mutagenicity in the Salmonella/mutagenicity assay. These results were almost identical with those of the DNA repair test except for several azo dyes such as AzB and 4,4'-(CH2Oacetyl)2AzB of the azobenzenes and N'-acetyl-4-amino-dimethylaminoazobenzene and N'-acetyl-N-methyl-4-amino-N-acetyl methylaminoazobenzene of the diaminoazobenzenes.
Mori
H
H
Mori
Y
Y
Sugie
S
S
Yoshimi
N
N
Takahashi
M
M
Ni-i
H
H
Yamazaki
H
H
Toyoshi
K
K
Williams
G M
GM
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism*; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011912:Rats, Inbred ACI; D012475:Salmonella / Q000187:drug effects; D013329:Structure-Activity Relationship; D004124:p-Dimethylaminoazobenzene
D001391:Azo Compounds; D009153:Mutagens; D004124:p-Dimethylaminoazobenzene; C009850:azobenzene