Glucosinolates: DNA Adduct Formation In Vivo and Mutagenicity In Vitro

摘要

~(32)P-postlabelling analysis indicated the time-dependent formation of five char-acteristic spots of adducts with the endogenous DNA in broccoli homogenates.One of these adduct spots was also consistently detected in tissues of rats and mice fed raw or steamed broccoli. Its structure was identified by mass spectro-metry and direct chemical synthesis. It was formed by a specific glucosinolate(GLS-A); administration of purified GLS-A or a degradation product formed from GLS-A by myrosinase (DEG-A) to mice led to the formation of the same DNA adduct as observed after feeding broccoli. However, when purified GLS-Awas used, adduct formation was largely restricted to the large bowel, whereas adducts were detected in many additional tissues after feeding broccoli or ad-ministering DEG-A. This difference may result from the enzymes mediating the first step of bioactivation: glycosidases from intestinal bacteria with puri-fied GLS-A, plant myrosinase in the case of broccoli; this activation step is not required with the DEG-A. Unlike other GLS, GLS-A was highly mutagenic to Salmonella typhimurium strains in the presence of myrosinase. It remains to be studied whether broccoli-induced mutagenic DNA adducts can induce tumour-igenesis.