ABSTRACT
The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by the rate of erythropoiesis in the bone marrow erythropoietin, a growth factor for the erythroblast, which was used to induce erythropoiesis. The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose-response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1-dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin. The effect of erythropoietin was maximal when erythropoietin was given 24 hr before DMH, indicating that accelerating the multiplication of erythroblasts will increase the frequency of micronuclei induced by mutagens. Induction of MPCE in the bone marrow by four other compounds--benzo(a)pyrene, 2-naphthylamine, mitomycin C, and vincristine--was also increased by pretreatment with erythropoietin.
Subject(s)
Erythropoietin/toxicity , Micronucleus Tests , Mutagens , 1,2-Dimethylhydrazine , Animals , Dimethylhydrazines/administration & dosage , Dimethylhydrazines/toxicity , Dose-Response Relationship, Drug , Drug Administration Schedule , Erythrocytes/ultrastructure , Male , Mice , Mice, Inbred BALB CABSTRACT
The genotoxicity of a variety of hydrazine derivatives was examined in the DNA-repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, i.e., N'-acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine.2HCl, 1-hydrazinophthalazine.HCl, methylhydrazine.sulfate, p,p'-oxybisbenzene disulfonylhydrazide and phenylhydrazine.HCl, elicited positive DNA repair responses in the test on rat hepatocytes. In the test on mouse hepatocytes, 4 more hydrazine derivatives, i.e., 1,1-dimethylhydrazine, hydrazine hydrate, hydrazine sulfate and 2-methyl-4-chlorophenoxyacetic acid hydrazide.HCl also generated positive responses, in addition to the 6 positive compounds in the rat assay. These results suggest that mouse hepatocytes are more susceptible to the genotoxicity of hydrazine derivatives, and that the species differences in genotoxicity appear to be in agreement with the in vivo carcinogenicity of these agents.
