Carcinogenic effects of ptaquiloside in bracken fern and related compounds

Consumption of the bracken fern Pteridium aquilinum by cattle has been show n to induce bladder and intestinal carcinomas in cattle and to cause a numb er of diseases in other farm animals. An unstable glucoside named ptaquilos ide, containing a reactive cyclopropane ring, has been isolated from the fe rn and its potent carcinogenicity proven. Nineteen of 31 ferns tested by ch emotaxonomic methods in japan have been found to contain potentially carcin ogenic ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum, Hydrolysis of ptaquilosides leads to pterosins; under milder conditions a d ienone which is believed to be the primary carcinogen is obtained. Hypacron e, a sesquiterpine containing a reactive cyclopropane ring, has been isolat ed from Hypolepis punctata and its structure proved by synthesis. Illudins, structurally similar to ptaquiloside, have been isolated from the basidiom ycete Omphalotus illudens. These give anti-tumour activity and similar reac tivity with nucleophiles to ptaquiloside. Compound CC-1065, a highly toxic antibiotic also containing a cyclopropane ring, has been isolated from Stre ptomyces zelensis, The mechanism of its reactivity with DNA has been compar ed to that of ptaquiloside and the small structural differences between car cinogenic and anti-tumour activity discussed. Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity have been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA, The reactivity of cys teine with ptaquilosides and illudins is discussed, as is the role of cyste ine alkylating agents in apoptosis. (C) 2000 Cancer Research Campaign.