Phenothiazine Inhibition of Intestinal and Urinary Bladder Tumors Induced in Rats by Bracken Fern<xref ref-type="fn" rid="FN2">2</xref>

Abstract

Bracken fern (Pteris aquilina), mixed with grain (1:3 by weight), was fed to 2 groups of male and female albino rats that also received 2 mg thiamine hydrochloride subcutaneously once weekly. In Group 1, fed this diet, 19 of 21 rats surviving more than 6 months developed intestinal neoplasms (adenomatous polyps or adenocarcinomas) and the same number developed urinary bladder tumors (papillomas or transitional cell carcinomas). In Group 2, of 28 rats fed the bracken-fern diet, to which phenothiazine (2 mg/g diet) was added, 11 had intestinal tumors and 10 had bladder tumors. The average survival of the rats in both groups was 11 months. Nine rats fed a grain diet containing no bracken fern developed neither intestinal nor bladder tumors. Rats receiving the phenothiazine-bracken fern diet had persistently increased levels of benzo[a]pyrene (BP) hydroxylase activity in the mucosa of the small intestine, liver, and kidney, whereas rats fed the bracken fern diet (Group 1) showed normal or only slightly elevated levels of this enzyme. The magnitude of induction, relative to untreated control rats, was highest in the kidney and similar for the mucosa of the small intestine and liver. BP hydroxylase activity of the small intestine progressively decreased in all groups of animals. These data are consistent with the possibility that phenothiazine-stimulated microsomal metabolism of the bracken fern partially inhibits the genesis of intestinal and bladder neoplasms. However, the possibilities of a direct chemical interaction between carcinogen and phenothiazine at some point before the active site, or of a competitive inhibition of the carcinogen by the drug at some critical binding site, cannot be excluded.