Abstract
Aspects of the toxicology of bracken (Pteridium aguilinum) were studied in sub-acute and chronic studies using male Wistar-albino rats. In a chronic study, bracken induced ileal adenomas in an 8.5 month period but after 24 months, no tumours were seen in both the quercetin- and shikimate-fed rats. Tissue ornithine decarboxylase (ODC) levels were enhanced over a 90-day test period when shikimate was fed alone or in conjunction with BBN and MNNG as initiators and with cyclophosphamide, saccharin and lithocholate as promoters, suggesting that shikimate might be a tumour promoter. Quercetin, was able to enhance ODC levels in conjunction with cyclophosphamide, BBN and MNNG as initiators and with cyclophosphamide, saccharin and lithocholate as promoters. However, it did not enhance tissue ODC levels when administered alone. Bracken, shikimate and quercetin induced a macrocytic, normochromic, non-regenerative anaemia with thrombocytopenia and granulocytopenia at the termination of the 90-day study.The bracken-induced ataxia of monogastrics was attributed additionally to nitrite and cyanide, due to the very high levels found in the urine and serum respectively of bracken-fed rats over a 28-day test period. The high urinary nitrite levels of the bracken-fed rats prompted an investigation into the role of N-nitrosation in bracken-induced carcinogenesis. To this end, the Nitrosation Assay period (NAP) revealed the presence of nitrosatable entities in the gut of the bracken-, quercetin- and shikimate-fed rats and in the urine of the bracken- and quercetin-fed rats. This suggests that nitrosation, probably via the formation of nitrosamides, might be an important mechanism for the mediation of bracken-induced carcinogenesis. The plausibility of explaining various aspects of the sub-acute and chronic toxicity of bracken in monogastrics and ruminants on the basis of a "nitrosamide hypothesis" is discussed.