| Project/Area Number |
09670358
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Osaka University |
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Principal Investigator |
TAKEUCHI Toru Osaka University Medical School, Lecturer, 医学部, 講師 (00188161)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Tatsuya Osaka University Medical School, Associate Professor, 医学部, 助教授 (20150310)
MORIMOTO Kanehisa Osaka University Medical School, Professor, 医学部, 教授 (20143414)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Reactive oxygen species / oxidative DNA damage / mutation / carcinogenesis / hprt |
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| Research Abstract |
Every life which depends on oxygen generates reactive oxygen species (ROS) in the body.ROS induce many kinds of damage, among which oxidative DNA damage is closely related to carcinogenesis.Oxidative DNA damage may induce mutations and the accumulation of the mutations may cause the cancer development.However no reports have described the mutagenicity and mutation spectra of randomly induced oxidative DNA damage in mammalian systems.In this study, using 8-hydroxydeoxyguanosine(8OHdG) as a marker of oxidative DNA damage, we evaluated the mutagenicity and mutation spectra of oxidative DNA damage in Chinese hamster V79 cell.
Using a photo-Fenton reagent(NP-III) and UVA irradiation, we could induce considerable amounts of 8OHdG and DNA strand breaks in V79 cell.We then studied the mutant frequency in hypoxanthine-guanine phosphoribosyltransferase (hprt) locus by 6-thioguanine (6-TG) resistance.NP-III and UVA induced dose-dependent increase in both 8OHdG and mutant frequency, however, the in
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crease in 8OHdG was greater than that in mutant frequency.We collected 6-TG resistant clones and studied how their hprt gene had been mutated.We extracted DNA and mRNA from the clones and analyzed their genomic and complementary DNA of hprt.Most of the mutants showed deletion and 2-base exchange at T : A sites.
From these results we conclude that randomly induced oxidative DNA damage may not be highly mutagenic at hprt locus and may induce mostly deletion type mutations.Oxidative DNA damage is considered highly mutagenic and 8OHdG is reported to induce G : C * T : A point mutation.These conclusion were drawn mainly from cell-free systems or bacteria with deficient to DNA repair enzymes.In our system 8OHdG was removed efficiently from the damaged DNA, thus oxidative DNA damage including 8OHdG might not induce mutant frequency and mutation spectra as expected.However, to draw a generalized conclusion in mammalian systems, we should study the effects of ROS on mutant frequency and mutation spectra in genes other than hprt. Less
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