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

✍ Scribed by Hatakeyama, Shigeki ;Hayasaki, Yayoi ;Masuda, Makihiko ;Kazusaka, Akio ;Fujita, Shoichi

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 719 KB
• Volume: 10
• Category: Article
• ISSN: 0887-2082
• DOI: 10.1002/jbt.2570100305

✦ Synopsis

Effect of the induction of drug metabolizing enzymes by Sudan I11 on the in vivo and in vitro genotoxicity elicited by 7,12-dimethylbenz(a1anthracene (DMBA) was investigated. A significant suppression of DMBA-induced micronucleated reticulocytes was observed in C57BL/6 mice treated with Sudan I11 intraperitoneally for 3 or 5 days before injection of the DMBA. However, the preincubation of DMBA with hepatic microsomes from Sudan 111-treated rats caused a marked increase in the in vitro mutagenicity in the Ames assay, paradoxically. Sudan I11 was found to induce CYP 1A1, 7-ethoxycoumarin 0-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 111-treated rats was inhibited by the addition of uridine 5'-diphosphoglucuronic acid or reduced glutathione with cytosol. Mutagenic metabolites of DMBA formed by CrPlAl appeared to be effectively detoxified by these phase I1 enzymes. The results of this study suggest that Sudan IIIinduced prevention of in vivo mutagenesis is due to the induction of both CYP 1Al and detoxifying phase I1 enzymes. The induced CYPlAl may accelerate formation of active metabolic intermediates, but phase I1 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.