Paradoxical effect of sudan III on the in vivo and in vitro genotoxicity elicited by 7,12‐dimethylbenz(a)anthracene

Abstract

Effect of the induction of drug metabolizing enzymes by Sudan III on the in vivo and in vitro genotoxicity elicited by 7,12-dimethyl-benz(a)anthracene (DMBA) was investigated. A significant suppression of DMBA-induced micronucleated reticulocytes was observed in C57BL/6 mice treated with Sudan III intraperitoneally for 3 or 5 days before injection of the DMBA. However, the preincubation of DMBA with hepatic microsomes from Sudan III-treated rats caused a marked increase in the in vitro mutagenicity in the Ames assay, paradoxically. Sudan III was found to induce CYP 1A1, 7-ethoxycoumarin O-deethylase activity as well as both UDP-glucuronyl transferase and glutathione S-transferase activities. The increase of mutagenicity of DMBA observed in the Ames assay using hepatic microsomes from Sudan III-treated rats was inhibited by the addition of uridine 5'-diphosphoglucuronic acid or reduced glutathione with cytosol. Mutagenic metabolites of DMBA formed by CYP1A1 appeared to be effectively detoxified by these phase II enzymes. The results of this study suggest that Sudan III-induced prevention of in vivo mutagenesis is due to the induction of both CYP 1A1 and detoxifying phase II enzymes. The induced CYP1A1 may accelerate formation of active metabolic intermediates, but phase II enzymes are also induced and detoxify these intermediates to inactive metabolites. This would reduce residence time of the carcinogen in the body and the time of exposure to active metabolites for target organs.

A Review of Cytotoxic Effects of Azo Dyes on Brain-subregion

“…Sudan dyes, an azo and diazo colors, are chemical materials widely utilized as colorants in foods, solvents, textiles, waxes, cosmetics, etc. The Sudan III is a member of the Sudan dye family, which has confirmation for use in cosmetic products that do not contact the mucus membranes due to its lipophilicity ( (59). Moreover, it could increase DMBA mutagenicity when hepatic microsomes from rats treated with Sudan III were used in the Ames.…”

In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research

“…The approaches to toxicity testing significantly differ among various categories of toxicity models. Consequently, it is challenging to gather information for a systematic comparison of the models (Figure 3) [32][33][34][35][36][37]. Moreover, heterogeneous endpoints may also be the reason for observed contradictory effects among the models [32][33][34]36,37] as well as for many drug approval failures (Table 1).…”