Induction of sister chromatid exchanges in murine colonic tissue

As cancers of the large bowel arise primarily in the epithelial cells of the colon, measurement of genetic damage induced in those cells may aid in elucidating contributing factors in the etiology of the disease. Accordingly, procedures for the in vivo measurement of sister chromatid exchanges (SCE) have been adapted for use with colonic cells. Agar-coated 5-bromo-2'-deoxyuridine (BrdUrd) tablets were implanted (s.c.) in mice and colonic tissue prepared for measurement of SCE 48 hr later. When mice were treated by intraperitoneal injection with 20 mg/kg 1,2-dimethylhydrazine (DMH), a colon carcinogen, a significant increase over control SCE frequencies was found when treatment with carcinogen occurred in the interval from 14 hr before to 36 hr following BrdUrd administration. Treatment with DMH 2 hr following implantation of BrdUrd produced a dose-dependent increase in SCE frequencies, with the highest dose (20 mg/kg) resulting in frequencies approximately twice those of controls. Dimethylhydrazine was not found to be effective in inducing SCE in bone marrow cells of mice. As SCE can be induced by carcinogens and mutagens, measurement of SCE in colonic epithelium may be useful in identifying potential colon carcinogens.