MODULATING EFFECTS OF ELLAGIC ACID, VANILLIN AND QUERCETIN IN A RAT MEDIUM-TERM MULTIORGAN CARCINOGENESIS MODEL

Effects of dietary supplementation with the antioxidants ellagic acid, quercetin and vanillin were examined using a medium term multi-organ carcinogenesis model in rats. Groups of 10-15 male F344 rats were give n i.p. injections of diethylnitrosamine (DEN, 100 mg/kg body wt.) and N-methylnitrosourea (MNU, 20 mg/kg body wt), s.c, injections of 1,2-di ethylnitrosamine (DMH, 40 mg/kg body wt.), together with 0.05% N-butyl -N-(4-hydroxybutyl)nitrosamine (BBN) and 0.1% 2,2'-dihydroxy-di-n-prop ylnitrosamine (DHPN), both in the drinking water, for a total multi pi e initiation period of 4 weeks (DMBDD treatment). Ellagic acid, querce tin or vanillin, each at a dose of 1% each in the diet were administer ed from 1 day before and throughout the carcinogen exposure period, or after completion of the initiation regimen. All surviving animals wer e sacrificed at the end of week 36, and major organs were examined his topathologically. In the small intestine, significant reductions in th e incidence and number of tumors (adenomas and carcinomas) were observ ed in the groups administered ellagic acid during (8%, 0.08 +/- 0.29) or after (8%, 0.08 +/- 0.29) DMBDD treatment, and those receiving quer cetin after DMBDD treatment (0%) compared to the control value (57%, 1 .07 +/- 1.21). Although the incidences were not statistically signific ant, slightly decreased numbers of small intestinal tumors were found in the groups receiving vanillin during (0.33 +/- 0.72), or after (0.4 0 +/- 0.83) DMBDD treatment. The incidence of large intestinal carcino mas in the group treated with vanillin during DMBDD treatment was sign ificantly higher (73%) than the control value (21%). These results ind icated that while ellagic acid and quercetin exerted potent chemopreve ntive action in both the initiation and promotion stages in the presen t experimental system, their beneficial effects were restricted to the small intestine. Since small intestinal carcinomas are very infrequen t in humans, the advantages of these phenolic compounds for human appl ication as chemopreventors should not be overestimated.