Azo Dye Liver Carcinogenesis: Reaction of Hydroxymethylaminoazobenzene with Nucleic Acids in vitro

Abstract

IN a long series of aminoazobenzene derivatives tested for hepatocarcinogenicity in the rat only those compounds with at least one N-methyl group are markedly active¹. The hypothesis has been advanced that the actual carcinogen is a derivative of the parent dye and that its production may be hindered or enhanced under different dietary conditions, or in different species. The N-methyl group is thought to undergo stepwise oxidation in the liver to formaldehyde, the first product being an N-methylol derivative, hydroxymethylaminoazobenzene (I) in the case of methylaminoazobenzene². Such compounds are reactive species and are capable of alkylating thiol groups, amino-groups, phenolic residues and so on by a Mannich condensation. It has been suggested that reactions of this type account to some extent for the formation of protein bound dye in vivo in the case of dimethylaminoazobenzene (butter yellow) and certain of its derivatives^1,3,4. In view of the importance of DNA and RNA in cellular metabolism, an investigation has been carried out to determine whether such methylol derivatives are capable of reacting with nucleic acids in vitro.