|Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Cigarette smoking causes many chronic diseases but is a preventable risk factor in developing countries. However, it may be possible to relieve the smoke induced damage by increasing the protective defense system. As vitamin C intake reduces smoking risk, it is recommended that smokers should take more vitamin C. However, the molecular mechanism of vitamin C intake on smokers has not been thoroughly investigated. We have found there to be suppression of smoke induced cytochrome P-450 1A1 (CYP1A1) mRNA expression by high dose ascorbic acid administration. Therefore, we surveyed other genes the expressions of which were altered by the administration of high dose ascorbic acid. As cigarette smoking increases oxidative stress, we investigated the effect on anti-oxidative enzymes expression. The Osteogenic Disorder Shionogi (ODS) rat which lacks ascorbic acid synthesis enzyme, were administered either minimal amounts (4mg/day, S4) or high dose amounts (40mg/day, S40) of ascorbic acid, and were exposed to cigarette smoke daily for 25 days. The effect on anti-oxidative enzymes mRNA expression in the liver was measured by competitive reverse transcription - polymerase chain reaction method (competitive RT-PCR). CuZn-superoxide dismutase (SOD), MnSOD, catalase and protein disulfide isomerase (PDI) were significantly decreased by high dose ascorbic acid administration, and plasma glutathione peroxidase was also decreased but not significantly. Cigarette smoke exposure slightly increased gene expression of PDI and catalase, but not significantly. The differently expressed 27 genes in the liver were found by differential display methods. From 27 genes, altered expression of plasma proteinase inhibitor alpha-1-inhibitor III and CYP1A2 were confirmed by competitive RT-PCR. These results show that ascorbic acid intake influences gene expression of anti-oxidative enzymes, an ascorbic acid recycle enzyme and xenobiotic metabolizing enzymes.