NIIKAWA Miki Gifu Pharmaceutical University, Department of Pharmacy, Assistant Professor, 薬学部, 助手 (80237643)
KITO Hideaki Gifu Pharmaceutical University, Department of Pharmacy, Assistant Professor, 薬学部, 助手 (90161512)
NAGASE Hisamitsu Gifu Pharmaceutical University, Department of Pharmacy, Associate Professor, 薬学部, 助教授 (40141395)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥1,400,000 (Direct Cost : ¥1,400,000)
The chemical prevention have become important with the increase of cancer, . There are various causes for the occurrence of cancer, . It is known that 8-hydroxy-2'-deoxyguanosine (8OHdG) production in DNA induces the mutation and cancer. Glu-P-1 and IQ are the pyrolysates of amino acids and protein, and are important substances for cancer production. There is a possibility that 8OHdG production is one of the causes of their ability of cancer production.
In this research, the production of 8OHdG by Glu-P-1 and IQ was investigated in vitro and in vivo, and the anti-DNA damaging substances were screened with the inhibition of 8OHdG production. The results are as follows.
1) HO-NH-Glu-P-1 and OH-NH-IQ,those are the active species of Glu-P-1 and IQ,induced the increase of 8OHdG in DNA of bacteria.
2) When OH-NH-Glu-P-1 or HO-NH-IQ was added to 2'deoxyguanosine (dG) in vitro, the increase of 8OHdG was observed. Then, chitin calcium, pyridoxine or hinokitiol was added to the reaction system and the inhibition of 8OHdG production was observed.
3) In vivo experiments, the significant increase of 8OHdG was observed in DNA of mouse liver at 48 hours after IQ injection.
4) 86,100 and 70% of inhibition ratios of the 8OHdG production were observed with 50 mg/kg of chitin calcium in liver DNA at pre-, simultaneous, post-administration, respectively. 28,100 and 16% ratios was observed by pyridoxine and 19,24 and 27% was done by hinokitiol.
By this results, the significant inhibition of 8OHdG production was observed with chitin calcium at various administration and the application to chemical prevention was expected.