SPECIFIC SPECIES OF INTESTINAL BACTERIA INFLUENCE THE INDUCTION OF ABERRANT CRYPT FOCI BY 1,2-DIMETHYLHYDRAZINE IN RATS

To shed Light on the association of intestinal microflora with the dev elopment of colon cancer, we studied the modifying effects of intestin al microflora on the occurrence of 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) in germfree (GF), gnotobiotic (GB) and conventionalized (Cvd) rats. In the first part of this study, 10 w eek old germfree Fischer-344 rats were randomly assigned to three grou ps and two groups of rats were orally inoculated with mixtures of pure culture of Escherichia coli, Enterococcus faecium, and several strain s of Bacteroides and Clostridium species (GB), or feces from conventio nal rats (Cvd). Inoculated rats were given two weekly i.p. injections of DMH (20 mg/kg body wt) at 13 and 14 weeks of age. Rats were sacrifi ced 11 or 34 weeks after the last DMH injection for ACF scoring. The t otal number of ACF, ACF with four or more crypts/focus, and mean numbe r of aberrant crypts per focus (crypt multiplicity) in GB rats sacrifi ced at week 34 were 168% (P < 0.001), 442% (P < 0.001) and 138% (P < 0 .001) of those in GF rats, respectively. On the other hand, the same v alues in Cvd rats were 42% (P < 0.001), 147% (P = 0.246) and 159% (P < 0.001) of those in GF rats, respectively Similar results were observe d in rats that were sacrificed at week 11. In the second part of this study, the effect of colonization of Bifidobacterium breve on the ACF profiles was examined in GB rats. The number of ACF with four or more crypts/focus and crypt multiplicity in GB plus B. breve rats at week I I were significantly lower than those of GB rats (P < 0.01, and P < 0. 05, respectively), although the former was not statistically significa nt at week 34. These findings suggest that some intestinal bacteria mi ght behave as promoters and some as anti-promoters in colon carcinogen esis. (C) 1997 Elsevier Science Ireland Ltd.