Modification of early dimethylhydrazine carcinogenesis by colonic mucosal hyperplasia

The interaction of colonic mucosal hyperplasia with early 1,2-dimethylhydrazine (DMH) carcinogenesis was studied in random-bred NIH Swiss mice utilizing hyperplasia-inducing Citrobacter freundii. Mice inoculated with this bacterium developed significantly more DMH focal atypia than did mice without hyperplasia following a single dose of DMH (20 mg/kg). Mice with hyperplasia also developed DMH focal atypia with diminished doses of DMH (10 and 5 mg/kg), while normal mice did not. The effect of C. freundii on early DMH carcinogenesis was shown to be due to the hyperplasia rather than to a direct interaction of the bacterium with DMH. Focal atypia arose in high incidence 1 month after a single dose of DMH (20 mg/kg) but did not appear to progress to later stages of neoplasia, since significantly fewer cases of atypia were present at 2 to 4 months among a randomized population. Colonic focal atypia may represent a reversible preneoplastic or precursor lesion as seen in other tissues, with features more aligned to neoplasia than to hyperplasia.