The distal colon and rectum from male F344 rats treated with 15 mg/kg 1,2-dimethylhydrazine · 2 HCl (DMH) for 20 weeks were analyzed for focal areas of enzyme alteration. Tissues were embedded in methacrylate at 4°C and cut in 2- to 4-µm serial sections. In DMH-treated rats, 8.8 ± 2.4 foci/cm2 of examined mucosa were observed at 20 weeks and 7.7 ± 1.1 foci/cm2 at 31 to 52 weeks, compared with 1.2 ± 0.6 foci/cm2 in control rats (P = 0.01). The number of foci at 31 to 52 weeks compared with 20 weeks did not change significantly, but the area of altered rectal mucosa increased from 0.22 ± 0.2% at 20 weeks to 1.47 ± 0.6% at 31 to 52 weeks (P = 0.051). Most foci had decreased N-acetyl-β-d-glucosaminidase, α-naphthyl butyrate esterase, and mucin in epithelial cells and increased γ-glutamyl transpeptidase in the stroma. Morphologically, the foci varied from normal to overtly dysplastic. Grossly, tumors were identified in 5 of 20 DMH-treated rats killed at 31 to 52 weeks but not in 12 DMH-treated rats killed at 20 weeks or 30 control rats killed at 20 to 52 weeks. These data suggest but do not establish that enzyme-altered foci are putative preneoplastic lesions in the colon.

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This work was supported by Grants R01 CA48032, R01 CA36467, R01 CA38727, and P30 CA43703 from the National Cancer Institute.

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