Comparison of the mutations induced by p-benzoquinone, a benzene metabolite, in human and mouse cells.
Benzene is one of the chemicals widely contaminating the environment. Benzene is suggested to be a human leukemogen. When benzene is absorbed in the human body, it is metabolized firstly in the liver and subsequently in the bone marrow where it provokes initiation of leukemia. In the present study, we analyzed mutations induced by p-benzoquinone (p-BQ), a benzene metabolite, in human cells using a shuttle vector plasmid pMY189, and compared frequencies, types and spectra of the mutations with those of the mutations previously revealed in mouse cells using a similar plasmid pNY200. We found that p-BQ induces mutations in human and mouse cells at similar frequencies but with different types of mutagenesis. The proportion of tandem base mutations was significantly lower in human cells than in mouse cells. Most base substitutions were induced in G:C base pairs in both human and mouse cells. However, the proportion of G:C-->C :G transversion is significantly higher in human cells. These findings indicate that the p-BQ-induced DNA damage in human and mouse cells is processed in a different manner, and that extrapolation of mice findings on experimental benzene carcinogenesis to human cancer risk assessment should be conducted carefully.
Nakayama
A
A
Department of Global Environment Engineering, Graduate School of Engineering, Yoshida-Hommachi, Sakyo-ku, 606-8501, Kyoto, Japan.
Koyoshi
S
S
Morisawa
S
S
Yagi
T
T
D000818:Animals; D001483:Base Sequence; D016227:Benzoquinones / Q000633:toxicity*; D004247:DNA; D004261:DNA Replication; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008969:Molecular Sequence Data; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D010957:Plasmids
D016227:Benzoquinones; D009153:Mutagens; C004532:quinone; D004247:DNA