Oxidative DNA damage following exposure to dimethylarsinous iodide: the formation of cis-thymine glycol.
The purpose of the present study was to elucidate the genotoxic mechanism of trivalent dimethylated arsenic, particularly the induction mechanism of oxidative stress in nuclear bases. Cis-thymine glycol was used as a biomarker of DNA oxidation damage. The treatment of thymine with dimethylarsinous iodide (DMI), a model compound of dimethylarsinous acid, induced the formation of cis-thymine glycol. This oxidative damage was induced via the production of dimethylated arsenic peroxide, but not via the production of superoxide anion or hydrogen peroxide. Trivalent dimethylated arsenic may thus play an important role in arsenic carcinogenesis through the induction of oxidative base damage.
Department of Biochemical Toxicology, Nihon University College of Pharmacy, 7-7-1 Narashinodai, Funabashi, 274-8555, Chiba, Japan. yamanaka@pha.nihon-u.ac.jp
Kenzo
K
Yamanaka
Mutsumi
M
Mizoi
Mariko
M
Tachikawa
Akira
A
Hasegawa
Mikio
M
Hoshino
Shoji
S
Okada
D002101:Cacodylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry*
C029389:thymine glycol; D002101:Cacodylic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D013941:Thymine