Abstract
Suppression of genetic mutation is expected to be an important method to inhibit the progression of disease such as cancer formation. Through studies on mechanisms of mutation events in cancer patients, we found an increased levels of glucose-regulated protein 78 (GRP78) expression in association with suppression of mutation in human cells irradiated with ultraviolet C (Pancreas, 36, e7-14, 2008). Then we were intrigued by the possibility that this carcinogen-induced mutation could be suppressed, via modulation of GRP78 expression, by agents such as foods.
We focused on Japanese miso, which is a fermented food that has formed an important part of the Japanese diet for over 1300 years. Little is known about the ability of miso to modulate mutability in human cells. We here examined to determine whether miso treatment results in increased GRP78 expression and suppression of UVC mutagenicity in RSa cells. Supernatants of water extracts of miso products and their components were tested. In the samples-treated cells, the amount of GRP78 increased, as estimated by RT-PCR and immunoblotting analysis, and the frequency of UVC-induced ouabain resistant mutation (OuaR) and K-ras codon 12-base substitution mutation decreased. This decrease was not observed in cells with downregulation of GRP78 by GRP78 siRNA transfection. The results suggest that miso suppresses UVC mutagenicity by enhancing GRP78 expression in human cells.
