DNA damage by ethylbenzenehydroperoxide formed from carcinogenic ethylbenzene by sunlight irradiation.
Ethylbenzene, widely used in human life, is a non-mutagenic carcinogen. Sunlight-irradiated ethylbenzene caused DNA damage in the presence of Cu2+, but unirradiated ethylbenzene did not. A Cu+ -specific chelator bathocuproine inhibited DNA damage and catalase showed a little inhibitory effect. The scopoletin assay revealed that peroxides and H(2)O(2) were formed in ethylbenzene exposed to sunlight. These results suggest that Cu+ and alkoxyl radical mainly participate in DNA damage, and H(2)O(2) partially does. When catalase was added, DNA damage at thymine and cytosine was inhibited. Ethylbenzenehydroperoxide, identified by GC/MS analysis, induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and caused DNA damage at consecutive guanines, as observed with cumenehydroperoxide. Equimolar concentrations of H(2)O(2) and acetophenone were produced by the sunlight-irradiation of 1-phenylethanol, a further degraded product of ethylbenzene. These results indicate a novel pathway that oxidative DNA damage induced by the peroxide and H(2)O(2) derived from sunlight-irradiated ethylbenzene may lead to expression of the carcinogenicity.
Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan.
Chitose
C
Toda
Takafumi
T
Uchida
Kaoru
K
Midorikawa
Mariko
M
Murata
Yusuke
Y
Hiraku
Yoshinori
Y
Okamoto
Koji
K
Ueda
Nakao
N
Kojima
Shosuke
S
Kawanishi
D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism*; D013472:Sunlight
D001555:Benzene Derivatives; D002273:Carcinogens; D010545:Peroxides; C041000:ethylbenzene hydroperoxide; D003300:Copper; D004247:DNA; C004912:ethylbenzene