Bracken-associated human and animal health hazards: Chemical, biological and pathological evidence

Bovine papillomavirus: opening new trends for comparative pathology

“…A similar pathology showing identical features was recently described in Turkish water buffaloes [24]. Several studies on bovine urothelial neoplasms reported the expression of cancer markers (reviewed by Gil da Costa et al [4]) such as calpain-3, recently proposed to contribute to carcinogenesis by cleaving pRB [25]. Bovine urinary bladder tumours are often of mesenchimal or mixed mesenchimal/epithelial origin, often involving the endothelium (haemangiomas, haemagiosarcomas).…”

“…Upon prolonged exposure to bracken (Pteridium spp., a carcinogenic fern) papillomas progress to squamous cell carcinomas, providing a useful example of viral and chemical co-carcinogenesis [30]. As recently reviewed by Gil da Costa et al, [4] malignant transformation seems to depend on the mutagenic and immunosuppressant properties of bracken toxins which, on the one hand, promote genomic instability, resistance to apoptosis and cell-cycle deregulation by inactivating p53 and activating ras and, on the other hand, prevent the immune system from clearing the viral papillomas (Figure 3). The bracken flavonoid quercetin, abundant in fruits and vegetables, also activates transcription from the BPV-4 long control region (LCR), up-regulating E7 expression and contributing to cell transformation in vitro [13].…”

“…However, the interaction between BPV and bracken is not as clear as in the gastrointestinal tract. In fact, ptaquiloside from bracken is capable of inducing pre-neoplastic and neoplastic bladder lesions in laboratory animals alone, without any viral involvement [4,31]. Bovine bladder tumours have attracted great interest not only due to their implication for animal health and the dairy industry, but also because they constitute a valuable spontaneous model to study the role of viral oncoproteins in cell transformation.…”

“…Research on BPV has led to most of the recent breakthroughs on the biology and pathology of animal papillomavirus, with major implications for human health. Using such spontaneous models, researchers have recently made significant discoveries on the interaction of papillomavirus with chemical carcinogens and immunosuppressants [4], on the role of BPV oncoproteins in cell transformation and immune evasion, on the infection of some unusual cell types and the possibility of haematogenous transplacental BPV transmission [5], as well as on new prophylactic and therapeutic vaccines [6][7][8].…”

Immunosuppressive effects ofPteridium aquilinumenhance susceptibility to urethane-induced lung carcinogenesis

“…The plant is known to produce distinct syndromes in livestock such as thiamine deficiency, acute hemorrhagic disease, and bright blindness (Smith, 2004). This fern is also well established as a carcinogen in humans and livestock through ingestion of plant crosiers (Abnet, 2007;Gil da Costa et al, 2012;Sugimura, 2000). Humans can be exposed to the plant indirectly through consumption of milk and meat from animals grazing on bracken fern (Alonso-Amelot & Avendano, 2002;Fletcher et al, 2011;Shahin et al, 1999) or through ingestion of contaminated water (Rasmussen et al, 2003).…”