Selective induction of micronuclei in the rat/mouse colon and liver by 1,2-dimethylhydrazine: a seven-tissue comparative study.
1,2-Dimethylhydrazine (DMH) was administered to both genders of mice and rats by oral gavage for 3 days. Twenty-four hours later, an assessment of the incidence of micronucleated cells was made in the bone marrow and sections of the gastrointestinal tract. An increase in micronucleated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stomach, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definition of the MTD precludes a definitive conclusion from being drawn. These results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogenic to rat and mouse liver and, although it is known to induce micronuclei in the hepatocytes of rats, no such data exist for the mouse. Consequently, 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. Thus, 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 the assays. These results indicate that the assessment of genetic toxicity in rodents should not rely solely on assays made in bone marrow.
Zhurkov
V S
VS
A.N. Sysin Institute of Human Ecology and Environmental Hygiene, Russian Academy of Medical Sciences, Moscow, Russia.
Sycheva
L P
LP
Salamatova
O
O
Vyskubenko
I F
IF
Feldt
E G
EG
Sherenesheva
N I
NI
D019813:1,2-Dimethylhydrazine; D000284:Administration, Oral; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D004064:Digestive System / Q000166:cytology / Q000187:drug effects*; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats
D004127:Dimethylhydrazines; D009153:Mutagens; D019813:1,2-Dimethylhydrazine