In vitro formation of organ-specific ultimate carcinogens of 4-dimethylaminoazobenzene and urethan by microsomes.
In order to determine the organ-specific carcinogenicity of 4-dimethylaminoazobenzene (4-DAB) and urethan, their metabolites formed in vitro by incubation with the microsomes from liver, lungs, brain and kidneys of rats were isolated by thin-layer chromatography. 4-DAB was found to be metabolized to give two major products, 4-aminoazobenzene and N-hydroxy-4-aminoazobenzene, only when incubated with liver microsomes. These metabolites were not detected when microsomal suspensions of lungs, brain and kidneys were used. Similarly, urethan was found to yield three metabolites, N-hydroxy derivative of ethyl carbamate, N-hydroxyvinyl carbamate, and epoxy derivative of ethyl carbamate, on incubation with lung microsomes, but not with the microsomes from liver, brain and kidneys. As the potential carcinogenic moieties were only formed by incubating these two compounds with the microsomes of their target organs, their organ-specific carcinogenicity may be explained.
Gupta
R
R
Department of Biochemistry, Panjab University, Chandigarh, India.
Dani
H M
HM
D000818:Animals; D001921:Brain / Q000378:metabolism; D002273:Carcinogens / Q000096:biosynthesis*; D002855:Chromatography, Thin Layer; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014520:Urethane / Q000378:metabolism*; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism*
D002273:Carcinogens; D014520:Urethane; D004124:p-Dimethylaminoazobenzene