Bracken carcinogens in the human diet.

The ubiquitous bracken fern (genus Pteridium) is the only higher plant known 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 addition, 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 degeneration and the myeloid aplasia) has been shown to be ptaquiloside (PT), a norsesquiterpene glucoside that can be present in bracken in extraordinary concentrations, up to 13 000 ppm. The highest concentrations were found in the crosiers and young unfolding fronds. The mutagenicity, clastogenicity, teratogenicity and carcinogenicity have been convincingly demonstrated. Under alkaline conditions the loss of the glucose gives rise to the formation of a dienone intermediate which possesses a highly reactive cyclopropyl ring capable of reacting with cellular macromolecules. PT has been shown to alkylate DNA at N3 of adenines in the minor groove, preferentially in 5'-TAG and 3'-A in 5'-AA-3' sequences. It also alkylates N7 guanines in the major groove occurring in 5'-TG sequences. It is believed that these alkylations lead to mismatch repair and subsequent mutations in particular proto-oncogenes. Recently a rat model of carcinogenesis has been established using intravenously (iv) administered PT. Some epidemiological evidence has indicated 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-infested areas. PT has been found in the milk of cows fed on bracken fern experimentally and the milk of bracken-fed cows has been shown to cause cancer in rats. PT carcinogenesis presents an excellent model of environmental and experimental carcinogenesis.