Catechol and hydroquinone have different redox properties responsible for their differential DNA-damaging ability.
We examined the redox properties of the "carcinogenic" catechol and the "noncarcinogenic" hydroquinone in relation to different DNA damaging activities and carcinogenicity using 32P-labeled DNA fragments obtained from the human genes. In the presence of endogenous NADH and Cu2+, catechol induces stronger DNA damage than hydroquinone, although the magnitudes of their DNA damaging activities were reversed in the absence of NADH. In both cases, DNA damage resulted from base modification at guanine and thymine residues in addition to strand breakage induced by Cu+ and H2O2, generated during the oxidation of catechol and hydroquinone into 1,2-benzoquinone and 1,4-benzoquinone, respectively. EPR and 1H NMR studies indicated that 1,2-benzoquinone is converted directly into catechol through a nonenzymatic two-electron reduction by NADH whereas 1,4-benzoquinone is reduced into hydroquinone through a semiquinone radical intermediate through two cycles of one-electron reduction. The reduction of 1,2-benzoquinone by NADH proceeds more rapidly than that of 1,4-benzoquinone. This study demonstrates that the rapid 1,2-benzoquinone two-electron reduction accelerates the redox reaction turnover between catechol and 1,2-benzoquinone, resulting in the enhancement of DNA damage. These results suggest that the differences in NADH-mediated redox properties of catechol and hydroquinone contribute to their different carcinogenicities.
Hirakawa
Kazutaka
K
Radioisotope Center, and Department of Hygiene, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Oikawa
Shinji
S
Hiraku
Yusuke
Y
Hirosawa
Iwao
I
Kawanishi
Shosuke
S
D002396:Catechols / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D009153:Mutagens / Q000494:pharmacology*; D010084:Oxidation-Reduction
D002396:Catechols; D006873:Hydroquinones; D009153:Mutagens; D004247:DNA; C034221:catechol; C031927:hydroquinone