Bracken carcinogens in the human diet

The ubiquitous bracken fern (genus Pteridium) is the only higher plant know n to cause cancer naturally in animals. In addition to the well-recognized syndromes of thiamine deficiency, acute haemorrhage associated with myeloid aplasia and blindness due to retinal degeneration, it causes neoplasia of the urinary bladder and in some circumstances, of the upper gut. In additio n, it has been shown to cause neoplasia in a wide range of tissues in many experimental species. The major carcinogen (and the cause of the retinal de generation and the myeloid aplasia) has been shown to be ptaquiloside (PT), a norsesquiterpene glucoside that can be present in bracken in extraordina ry concentrations, up to 13000 ppm. The highest concentrations were found i n the crosiers and young unfolding fronds. The mutagenicity, clastogenicity , teratogenicity and carcinogenicity have been convincingly demonstrated. U nder alkaline conditions the loss of the glucose gives rise to the formatio n of a dienone intermediate which possesses a highly reactive cyclopropyl r ing capable of reacting with cellular macromolecules. PT has been shown to alkylate DNA at N3 of adenines in the minor groove, preferentially in 5'-TA G and 3'-A in 5'-AA-3' sequences. It also alkylates N7 guanines in the majo r groove occurring in 5'-TG sequences. It is believed that these alkylation s lead to mismatch repair and subsequent mutations in particular proto-onco genes. Recently a rat model of carcinogenesis has been established using in travenously (iv) administered PT. Some epidemiological evidence has indicat ed higher risk of cancer in people who consume bracken crosiers, people who consume milk of cows feeding on bracken and those who live in bracken-infe sted areas. PT has been found in the milk of cows fed on bracken fern exper imentally and the milk of bracken-fed cows has been shown to cause cancer i n rats. PT carcinogenesis presents an excellent model of environmental and experimental carcinogenesis. (C) 1999 Elsevier Science B.V. All rights rese rved.