Mutagenesis vol. 19 no. 2 pp. 91-97,
March 2004
© 2004 UK Environmental Mutagen Society/Oxford University Press
Comparison of mutagenic potentials and mutation spectra of benzene metabolites using supF shuttle vectors in human cells
1Department of Global Environmental Engineering, Graduate School of Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan 2Division of Radiobiology and Environmental Science, Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1–2 Gakuen-cho, Sakai-city, Osaka 599-8570, Japan
Benzene is a human leukemogen and the metabolites are thought to be deeply involved in benzene leukemogenesis. In a previous study we reported the molecular analysis of p-benzoquinone (p-BQ) mutagenesis by using a supF shuttle vector plasmid and here we report the mutagenesis of the other metabolites, hydroquinone (HQ) and trans, trans-muconaldehyde (MUC). HQ is a precursor of p-BQ and MUC is produced by a ring-opening metabolic pathway. We found that the HQ redox cycle produced an oxidative lesion in plasmid DNA and significant differences among the mutagenic potentials of MUC, HQ and p-BQ. HQ has stronger mutagenicity than the others. It is about 20 and 600 times stronger than p-BQ and MUC, respectively. Furthermore, we found notable differences in each mutational feature. The MUC mutational type was characterized by a high frequency of tandem base substitutions that could be due to crosslinks produced by its aldehyde moieties, while HQ was characterized by frequent deletion. This HQ feature is the same as in vivo benezene mutagenesis of Big Blue mice reported by Provost et al. in 1996 and is also quite similar to a hydrogen peroxide mutational feature. Therefore, we presume that HQ and reactive oxygen species may play an important role in benzene carcinogenesis.
3To whom correspondence should be addressed. Tel: +81 75 753 5156; Fax: +81 75 753 5066; Email: nakayama{at}risk.env.kyoto-u.ac.jp
Received on April 3, 2003; accepted on November 17, 2003