Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum)

Albino noninbred weanling male and female rats were fed a basic grain diet (Group 1) or a basic diet supplemented with 33% bracken fern [BF (Group 2)] or 0.1% quercetin [purity, > 99% (Group 3)] for 58 weeks. The quantities of quercetin and kaempferol (a close structural analog) in BF as glycosides were determined to be 0.57 and 1.1 g, respectively, per kg of dried BF. Estimated mean total cumulative doses (mmol) per rat were: Group 1, quercetin, males and females < 0.03; kaempferol, males and females < 0.03; Group 2, quercetin, males 5.8, females 5.2; kaempferol, males 11.9, females 10.8; and Group 3, quercetin, males 27.8, females 25.3; kaempferol, males and females < 0.03. Growth of rats fed BF or quercetin was comparable but significantly (p < 0.01) slower after 24 weeks than that of Group 1. Mean survivals (weeks) of rats of all groups were: Group 1, 58 +/- 7 (S.D.); Group 2, 51 +/- 13; and Group 3, 56 +/- 8. They were not significantly different, although rats fed BF tended to die earlier secondary to intestinal tumor-induced intussusception and obstruction. The following incidences of intestinal or bladder neoplasms in male or female rats, respectively, were observed: Group 1, intestinal and bladder, males, 0 of 9, females, 0 of 10; Group 2, intestinal, males, 7 of 8, females, 10 of 11; bladder, males, 6 of 8, females 8 of 11; Group 3, intestinal, males, 6 of 7, females, 14 of 18; bladder, males, 2 of 7, females, 3 of 18. The histopathology of neoplasms of the 2 target organs was identical for rats of Groups 2 and 3. Multiple ileal intestinal neoplasms of rats fed quercetin included: adenoma, 4; fibroadenoma, 7; and adenocarcinoma, 9 (with mesenteric metastases, 3). The 5 bladder tumors were papillary or sessile transitional cell carcinomas.