A new class of potential carcinogenesis inhibitors: hindered p-benzoquinones

The investigation of the mechanisms of action by which phenolic antioxidants (i.e. BHA, BHT, etc.) protect DNA against interaction with activated BaP, led us to the finding that oxidated aminophenols are much more potent in this respect, being also powerful inhibitors of cytochrome P-450 dependent monooxygenases. However, the quinoneimine structures probably involved in this effect are chemically unstable reactive species and therefore difficult to handle. Based on these observations, we extended this study on several types of benzoquinones. We demonstrated that 2,6-di-t-butylbenzoquinone exerted a very good protective effect at DNA level (in standard conditions) as compared to the "classical" BHA (i. e. 91.3% and 34.4%, respectively). This hindered quinone is nontoxic (DL50 = 3085 mg/kg b. w.) and also did not exhibit inhibitory activity against GST. In contrast, the nonsubstituted p-benzoquinone is a powerful inhibitor of this last enzyme. Recently, 2,6-di-t-butylbenzoquinone was isolated from mutagenic depressing food and was considered one of the factors responsible for this effect.