ANTICARCINOGENIC ACTIVITY OF 6-METHYLSULFINYLHEXYL ISOTHIOCYANATE, ANACTIVE ANTIPROLIFERATIVE PRINCIPAL OF WASABI (EUTREMA-WASABI MAXIM.)

Synthetic 4-methylsulfinylhexyl isothiocyanate (MITC)(a potent inducer of phase 2 detoxification enzymes from broccoli) and 6-MITC(a potent anti-proliferative principal from wasabi) slightly inhibited the induc tion of mouse skin tumor in a two-stage process of carcinogenesis (ini tiator, 9,10-dimethyl-1,2-benzanthracene; promotor,12-o-tetradecanoylp horbol-13-acetate), but the effect was not significant. Both compounds , however, significantly inhibited the mutation of skin resulting from topical applications of the carcinogens. When a murine hepatoma cell line, Hepa 1c1c7, was treated with 2-, 4-, 6- and 8-MITCs, they augmen ted the induction of its quinone reductase, one of the phase 2 detoxif ication enzymes in a concentration dependent manner, and the 4- and 6- MITCs were much more potent on the reduction of the enzyme than the 2- and 8-MITCs. All 2-, 4-, 6- and 8-MITCs suppressed the growth of muri ne tumor cells, their suppressive activities being proportional to the length of their methyl residue. They were also cytotoxic to mouse per itoneal exudate macrophages which were not proliferating in vitro, ind icating that the cellular targets of isothiocyanate may not be depende nt upon the cell cycle. In addition, all the 2-, 4-, 6- and 8-MITCs in hibited the production of nitric oxide (a potent radical carcinogen) b y peritoneal macrophages.