SELECTIVE INDUCTION OF MICRONUCLEI IN THE RAT MOUSE COLON AND LIVER BY 1,2-DIMETHYLHYDRAZINE - A 7-TISSUE COMPARATIVE-STUDY/

1,2-Dimethylhydrazine (DMH) was administered to both genders of mice a nd rats by oral gavage for 3 days. Twenty-four hours later, an assessm ent of the incidence of micronucleated cells was made in the bone marr ow and sections of the gastrointestinal tract. An increase in micronuc leated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stoma ch, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definit ion of the MTD precludes a definitive conclusion from being drawn. The se results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogeni c to rat and mouse liver and, although it is known to induce micronucl ei in the hepatocytes of rats, no such data exist for the mouse. Conse quently, mice were administered DMH on 13 successive days, followed by 2/3 partial hepatectomy and assessment of micronucleated hepatocytes. A strong positive liver micronucleus assay response was observed. Thu s, DMH selectively induces micronuclei in the colon and liver of rats and mice, consistent with its carcinogenicity to these two tissues. No qualitative differences between the genders was observed in any of th e assays. These results indicate that the assessment of genetic toxici ty in rodents should not rely solely on assays made in bone marrow.