Induction of hepatic glutathione transferase and suppression of 7,12-dimethylbenz[a]anthracene-induced chromosome aberrations in rat bone marrow cells by Sudan III and related azo dyes.
Noninbred Long-Evans rats fed the reduced form of glutathione (GSH) 2 hours before injection with 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6)] showed a significant suppression of DMBA-induced chromosome aberrations (CA) in bone marrow cells. However, rats given injections of ethyl maleate [(EM) CAS: 141-05-9; (z)-2-butenedioic acid diethyl ester] 0.5 or 2 hours before being killed showed a remarkable fall in the hepatic GSH level. Furthermore, the administration of EM and bromosulfophthalein [CAS: 71-67-0; 3,3'-(4,5,6,7-tetrabromo-3-oxo-1(3H)-isobenzofuranylidene) bis(6-hydroxy)benzenesulfonic acid disodium salt] shortly before the DMBA injection inhibited the suppressive effects of Sudan III on DMBA-induced CA. A clear positive correlation was found between the capacity of Sudan III and related azo dyes to protect against DMBA-induced CA in bone marrow cells and glutathione transferase (GST) activity toward 1-chloro-2,4-dinitrobenzene in the liver cytosol induced by these azo dyes. DMBA activation with hepatic S-9 obtained from rats treated by polychlorinated biphenyls (PCB), phenobarbital, and Sudan III in the Ames system was high in this order as was also the case for the cytochrome P450 content. The addition of GSH to the Ames system containing S-9 from PCB-treated rats resulted in a substantial loss in the mutagenicity of DMBA. The present results suggest that GST and GSH play important roles in DMBA inactivation in rats previously administered Sudan III.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002869:Chromosome Aberrations; D004396:Coloring Agents / Q000494:pharmacology*; D004790:Enzyme Induction; D005978:Glutathione / Q000494:pharmacology; D005982:Glutathione Transferase / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D013194:Staining and Labeling
D001391:Azo Compounds; D001551:Benz(a)Anthracenes; D004396:Coloring Agents; D015127:9,10-Dimethyl-1,2-benzanthracene; D005982:Glutathione Transferase; D005978:Glutathione; C033006:sudan III