|Budget Amount *help
¥13,600,000 (Direct Cost : ¥13,600,000)
Fiscal Year 1999 : ¥7,500,000 (Direct Cost : ¥7,500,000)
Fiscal Year 1998 : ¥6,100,000 (Direct Cost : ¥6,100,000)
In addition to two type of substances which had been isolated as bioantimutagens against UV-induced mutation in Escherichia coli, (+) -gallocatechin (GC) from young guava leaves and methylmethane-thiosulfonate(MMTS) from califlower buds, new bioantimutagenic compounds (2,4-nonadienal and benzylaldehydes) have been isolated from a traditional Kyoto-vegetable, Hushimi sweet pepper. Interestingly, it has been further found that methyl salicylate (MS) showsa synegistic activity in the same system, Then, we have been interested in molecular function of these bioantimutagens in bacteria cells and higher animal cells.
No significant difference in genome DNAs prepared from between UV-irradiated bacteria cells, without or with a bioantimutagen, and control cells has been detected by ELISA procedure using a specific antibody against pyrimidine dimers in DNA.It is suggested that the function of the bioantimutagens (MMTS, 24ND, BA and GC) is not related to a excision repairing system in the cells after UV irradiation.
We prepared several chimeric plasmids having a reporter gene (lacZ) and each promoterregion from five different genes (uvrA, umuDC, ssb, sulA) , which involves in a SOS repairing system and determined the enzymatic activity after UV irradiation without or with a bioantimutagen. Decreased levels of transcripitional activity in umuDC genes have been observed when some of bioantimutagens were addeded. One of functions of these bioantimutagens (MMTS, 24ND, and cinnamaldehyde) is speculated to decrease the transcripitional levels of umuDC genes which lead to lowering errors in DNA replication.
Using human fibroblast cells function of these bioantimutagens has been studyed. MMTS and MA showed slight difference in transcriptional activity of NFAT and SRE signal transduction pathways 12 hrs after bioantimutagen treatment ; 1.5 and 1.4 times higher to those in no-treated cells.