Mutagenicity and cytotoxicity of naphthoquinones for Ames Salmonella tester strains
- Eisai Co., Ltd., Tsukuba-shi (Japan)
The molecular mechanisms involved in quinone cytotoxicity, especially mutagenicity, are still largely unknown. In order to better understand the molecular aspects of the mechanisms of quinone mutagenicity and cytotoxicity, we examined them by using a series of 13 simple structural naphthoquinone (NQ) derivatives for 9 Ames Salmonella mutagenicity tester strains in the presence or absence of liver homogenate S9 mix from rats induced with phenobarbital and 5,6-benzoflavone. Most NQs used in this study showed mutagenicity with and/or without S9 mix. The most potent mutagenic NQ was 2,3-dichloro-1,4-NQ, with mutagenicity of 18 induced revertents/nmol/plate for strain TA104 without S9 mix. Among the strains used, TA104, which is sensitive to oxidative mutagens, was the most sensitive to the NQs, and the second most sensitive strain was TA2637, which detects bulky DNA adducts. The relationship of mutagenic potency to the one-electron reduction potential with TA104 suggested that the higher redox potential NQs were more mutagenic than the lower redox potential NQs. The cytotoxic effect of the NQs was largely dependent on the structures of their substituents. It was suggested that the higher redox potential NQs were more cytotoxic than the lower redox potential NQs for all of the strains used, in contrast to the mutagenicity of the NQs. The presence of S9 mix decreased the cytotoxic effect of the NQs, the extent of which was also largely dependent on the structures of their substituents and is in accordance with the order of the height of the one-electron reduction potentials. These results indicate that the mutagenicity of NQs in Salmonella typhimurium was due to oxidative damage produced with activated oxygen species such as hydroxy radical and superoxide anion radical, which are generated as a result of the reduction of the NQs, and to bulky NQ-DNA adducts accounting for their electrophilic property, whose contribution was largely dependent on the substituents of NQs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 45255
- Journal Information:
- Chemical Research in Toxicology, Vol. 7, Issue 4; Other Information: PBD: Jul-Aug 1994
- Country of Publication:
- United States
- Language:
- English
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