1,2-Dimethylhydrazine (
DMH) is a potent colon
carcinogen that is commonly used as an initiator in studies of the effects of diet on
colon cancer. Previous studies have shown that although this compound produces multiple
tumors in the colons in most individuals of every species tested, it is, at best, marginally mutagenic in the bone marrow (micronuclei) and small intestine (Dlb-1 mutations). Here we report its mutagenicity in the primary target tissue, the colonic epithelium, by means of the Mutatrade markMouse cII assay, an assay for intragenic mutations in a lambda shuttle vector that is integrated into the genome of these mice. Animals were treated with 0, 10, 20, or 30 mg/ml of
DMH, either as a single injection or as multiple weekly
injections, and mutations were measured in both the small intestine and colon. In the small intestine, there was an increase in mutant frequency following a single injection of
DMH, but this was significant only at 30 mg/kg [induced mutant frequency (MF) = 18 x 10(-5) mutants/plaque]. In the colon, following a single treatment of
DMH, there was a significant increase in mutant frequency at doses of 20 and 30 mg/kg (induced MF = 17 x 10(-5) and 23 x 10(-5) mutants/plaque, respectively). Following ten
injections of 20 mg/kg of
DMH, there was a greater than ten-fold increase in mutations in the colon (MF = 275 x 10(-5) mutants/plaque) than the small intestine (MF = 25 x 10(-5) mutants/plaque). These results show that
DMH, under the conditions typically used for dietary studies, induces large numbers of mutations in the tissue in which it induces most
cancers.