|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
As a method to evaluatesafety in cancer chemoprevention, we have investigated whether antioxidants have the ability of the human DNA damage, using human cultured cells and 32P-labeledisolated DNA fragnrents of the human p53 tumor suppressor gene and c-Ha-ras-l prctooncogene. For detection of ce1lularDN.A damage, human cultured celles were treated with antioxidants, and examined by the pulsed-field get electrophoresis method. As the result. celularDNA damage was detected by the treatment of vitamin A, retinal, alpha-tocopherol and quercetin. Furthermore. we measured 8-hydroxy deoxyguanosine (8-OH-dG) formation, which was an index to an oxidative DNA lesion, quaruitativelyby HPLC-ECD.lntracellu1ar8-OH-dG formation significantly increased in cells treated with vitamin A, retinal and N-acetylcysteine. For detection of damage to isolated DN.A, antioxidants were incubated with 32P-labled DNA fragment in the presence of metalions, and the autoradiogram was obtained. alpha-Tocopherol, vitamin A, retinal, quercetin and N-acetylcysceine caused site-specific DN,A-damage in the presence of Cm(II). Catalase and bathocuproine. a Cu(I)-specific chelaror. inhibited the Co(II)-mediated DNA damage, suggesting the involvement of H_2O_2 and Curl).The DNA cleavage was observed frequency at thymine and cytosine residues in the presence of Cu(II).
So-called "antioxidants" act as antioxidants in some circumstances, but also act as prooxidants in other circumstances. In another word, antioxidants become to have ability of damaging DNA in some cases, although antioxidants protect from oxidative stress in other cases. These oxidative DNA damage could be responsible for initiation and/or tumor promotion the multi-stage of carcinogenesis. In is requested chat safety and efficacy should be estimated before recommending use of antioxidants for cancer chemopreventton.